International Conference on Emerging Trends in Drug Discovery and Development (ICETD3-2022)

20 Jan 2022, 08:30 → 21 Jan 2022, 19:00 Asia/Kolkata

Birla Institute of Technology

Swastika Ganguly (Birla Institute of Technology, Mesra)

A web-based event

A TWO-DAY SUMMIT OF TALKS, ACTIVITIES, AND WORKSHOPS

Abstract submission guidelines

Abstract template

Thursday, 20 January

Inaugural Ceremony

8.45-8.55 AM: Welcome Address: Prof. Papiya Mitra Muzumder
8.55-9.05 AM: Institute Prayer
9.05-9.20 AM: Address by Patron: Prof. Indranil Manna
9.20-9.35 AM: Address by Chairperson: Prof. Swastika Ganguly
9.35-9.45 AM: Vote of Thanks: Dr. Neelima Sharma

Conveners: Papiya Mitra Mazumder (Birla Institute of Technology, Mesra) , Trishna Bal (Birla Institute of Technology, Mesra)

Keynote Lecture: Session 1

Conveners: Papiya Mitra Mazumder (Birla Institute of Technology, Mesra) , Trishna Bal (Birla Institute of Technology, Mesra)

1 Phytocompounds in drug discovery and development: Control of cancer and antibiotic resistance

Herbal medicine is widely used globally to treat various diseases. Even though it does not lead to an immediate cure, the side effects are less compared to allopathic medicine. Cancer is one of the dreadful diseases killing millions of people worldwide. Antibiotic resistance is the major problem to tackle now as resistance had developed to many antibiotics. Discovery of new antibiotics is very much delayed. In both the problems herbal medicine comes as a remedy. Literature shows that there are phytocompounds which can control/cure various types of cancer and also some of them act alone as antibacterials or act as adjuvants along with the resistant antibiotics in reversing the antibiotic resistance. The presentation will cover the research outcome related to the above two problems based on the work carried out in herbal medicine for the past 15 years. Details will be presented on the role of a phytocompound from a rhizome in treating colon cancer, breast cancer and lung cancer. Some novel herbs will be discussed. To validate the above said properties of the herbs, molecular docking had also been carried out for the related phytocompounds with relevant targets along with the drugs being used to treat the ailments.

Speaker: Prof. Velmurugan Devadasan (University of Madras (Guindy Campus), Madras)

11:30 Tea Break

2 New herbal drug discovery for sickle cell disease: From ethnopharmacological claims to commercialization

Sickle cell disease is an inherited blood disorder that affects red blood cells. People with sickle cell disease have red blood cells that contain mostly hemoglobin S, an abnormal type of hemoglobin. The most common being Sickle Cell Anemia (SS), Sickle-Hemoglobin C Disease (SC), Sickle Beta- Plus Thalassemia and Sickle Beta-Zero Thalassemia. Health maintenance for patients with sickle cell disease starts with early diagnosis, preferably in the newborn period and includes penicillin prophylaxis, vaccination against Pneumococcus bacteria and folic acid supplementation. Patients frequently experience a vicious circle of events called a "Sickle cell disease crisis", in which low oxygen tension in tissue causes sickling, which leads to ruptured RBC and further leads to a serious decrease in RBC count and more sickling which often causes death. In search for a substance that can prevent red blood cells from sickling without causing harm to other parts of the body, hydroxyurea was found to reduce the frequency of severe pain, acute chest syndrome and the need for blood transfusions in adult patients with sickle cell disease. The health care cost of the management of sickle cell disease patients is disproportionately high compared to the number of people afflicted by the disease. Poor people cannot afford the high cost of treatment. Due to the debilitating effect and cost of managing sickle cell disease, research has been ongoing to determine the efficacy of the use of medicinal plants to tackle the multiple challenges presented in sickle cell disease. It is therefore evident that there is a very high need of new drugs which must have low toxicity and marked antisickling activity. Literature survey revealed many plants having significant antisickling and some of them are used by medical practitioners in certain parts of the world for treating Sickle cell anemia. However, despite the long-standing problem of sickle cell disease, the above information did not lead to the development of a standardized remedy for the treatment and management of Sickle cell anemia. The Research work discussed herewith comprises the development of an effective pharmaceutical dosage composition of the Wrightia tinctoria family Apocyanaceae, seeds extract for the treatment and management of Sickle cell disease. The studies include acute and sub-acute toxicity studies, Antisickling assay, and the further clinical studies of the formulation. The success story of the new drug discovery using the traditional Indian medicinal plant and its ethnomedical history has been unraveled in detail.

Speaker: Prof. Vinod Rangari (Guru Ghasidas University, Bilaspur)

12:45 Lunch Break

Keynote Lecture: Session 2

Conveners: Barij Nayan Sinha (Birla Institute of Technology, Mesra) , Neelima Sharma (Birla Institute of Technology, Mesra)

3 A new similarity-based read-across algorithm for the prediction of small datasets: Case studies with nano-toxicity data

Nanotechnology is an important area of science developed in 21$^{st}$ century, and it is being further advanced with time. Various new and modern technologies are utilized to produce different nanomaterials and nanoparticles now-a-days, and these are used in various fields of industries and society. Due to their random use, the nanomaterials are dumped improperly affecting the environment adversely. They can pass the plasma membrane with ease due to their small particle size and hence can cause toxicity also. The regulatory agencies are working continuously to assess the risk associated with the nanoparticles and nanomaterials. They rely mostly on the computational toxicity prediction to avoid the complexities associated with laboratory experimentation. QSAR and Read across are mostly used to fill the data gaps and for the risk and hazard assessment. In the present communication, we discuss a new similarity based read-across algorithm for the prediction of toxicity (biological activity in general) of untested compounds from structural analogues. Three similarity estimation techniques such as, Euclidean distance based similarity, Gaussian kernel function similarity, and Laplacian kernel function similarity are used in this algorithm. The new algorithm is properly validated against three published nanotoxicity datasets. The quality of predictions depends on the selection of the distance threshold, similarity threshold, and the number of most similar training compounds. In this work, best predictions were obtained after selecting 0.4 – 0.5 as the distance threshold, 0.00 – 0.05 as the similarity threshold, and 2– 5 as the number of most similar training compounds. After toxicity prediction of test set compounds, the external validation metrics such as Q 2 ext_F1 , Q 2 ext_F2 , RMSEp were calculated. The computed metric values clearly justify the efficiency of the new read-across method and accuracy of the generated data by the proposed algorithm. A java based computer program (available at https://sites.google.com/jadavpuruniversity.in/dtc-lab- software/home) has also been developed based on the proposed algorithm which can effectively predict the toxicity of unknown NPs after providing the structural information of chemical analogues. The new algorithm and the program can be used for the data gap filling, prioritizing existing and new NPs, and for the risk assessments of NPs.

Bibliography:

1. Chatterjee M, Banerjee A, De P, Gajewicz-Skretna A, Roy K. (2022) A novel quantitative read-across tool designed purposefully to fill the existing gaps in nanosafety data. Environ Sci: Nano DOI: https://doi.org/10.1039/D1EN00725D

Speaker: Prof. Kunal Roy (Jadavpur University, Kolkata)

16:00 Tea Break

4 NSAIDs’ antimicrobial mechanisms of action by inhibiting drug efflux and biofilm formation

The rise of antimicrobial drug resistance (AMR) in tuberculosis (TB) and non-tubercular mycobacterial (NTM) infection coupled with the shortage of new antibiotics has elevated the global infectious disease to a major global health priority. Our studies revealed that carprofen, a non-steroidal anti-inflammatory drug (NSAID), inhibited the growth of replicating, non-replicating and multi-drug-resistant clinical isolates of M. tuberculosis. We have approached to investigate the mechanism through which NSAIDs eliminate the infection. Integrative molecular and microbiological inquiries showed that carprofen, a bactericidal drug, inhibited bacterial drug-efflux mechanisms. Carprofen also restricted mycobacterial biofilm-like growth, highlighting the requirement of efflux-mediated communicative systems for the formation of biofilms. Transcriptome profiling revealed that carprofen likely acts by targeting fundamental molecular machine through the disruption of membrane potential, which may explain why spontaneous drug-resistant mutants could not be isolated in laboratory practice due to the pleiotropic nature of carprofen’s anti-tubercular action. This immunomodulatory drug has the potential to reverse TB antimicrobial drug resistance, offering a prospective path to clinical trials of novel chemotherapeutic combinations.

Bibliography:

1. Maitra A, Evangelopoulos D, Chrzastek A, Martin LT, Hanrath A, Chapman E, Hailes HC, Lipman M, McHugh TD, Waddell SJ, Bhakta S.* (2020) Carprofen elicits pleiotropic mechanisms of bactericidal action with the potential to reverse antimicrobial drug resistance in tuberculosis. J Antimicrob Chemother 75(11):3194-3201. DOI: https://doi.org/10.1093/jac/dkaa307

2. Lee C, Bhakta S. (2021) The Prospect of Repurposing Immunomodulatory Drugs for Adjunctive Chemotherapy against Tuberculosis: A Critical Review. Antibiotics (Basel) 10(1):91. DOI: https://doi.org/10.3390/antibiotics10010091

3. Maitra A, Bates S, Shaik M, Evangelopoulos D, Abubakar I, McHugh TD, Lipman M, Bhakta S. (2016) Repurposing drugs for treatment of tuberculosis: a role for non-steroidal anti-inflammatory drugs. Br Med Bull 118(1):138-48. DOI: https://doi.org/10.1093/bmb/ldw019.

4. Danquah, C.A.; Maitra, A., Gibbons, S., Faull, J and Bhakta, S. (2016) HT‐SPOTi: a rapid drug susceptibility test (DST) to evaluate antibiotic resistance profiles and novel chemicals for anti‐infective drug discovery. Curr Protoc Microbiol 40 (1), 17.8.1-17.8.12. DOI: https://doi.org/10.1002/9780471729259.mc1708s40

Speaker: Prof. Sanjib Bhakta (University College of London, Birkbeck)

5 Extraction of Naturally Occuring Cannabinoids : Recent Advances

Cannabinoids are the compounds that bind to cannabinoid receptors (endocannabinoid system), and they are one of the most-investigated groups of natural products. Cannabis sativa L. (family: Cannabaceae), an herbaceous medicinal plant from Central Asia, produces most of the ca. 150 naturally occurring cannabinoids, which are commonly known as ‘phytocannabinoids’. Among them, Δ9-tetrahydrocannabinol (Δ9-THC or simply, THC) and cannabidiol (CBD) are the two major cannabinoids. Δ9-THC mainly contributes to the psychoactive property of C. sativa, whereas CBD displays antipsychoactive property. A few other plants are also known to produce cannabinoids, for example, Acmella oleraceae, Echinacea angustifolia, Echinacea purpurea, Helichrysum umbraculigerum and Radula marginate. There are several methods available for the extraction of natural cannabinoids from various matrices, e.g., plant materials, medicinal and cosmetic products and human biological samples. In addition to classical maceration with organic solvents, several other methods like pressurized solvent extraction, solvent heat reflux, Soxhlet extraction, supercritical fluid extraction, ultrasound-assisted extraction and microwave-assisted extraction, are now routinely used nowadays for the extraction of cannabinoids. However, the choice of any extraction method, among other things, depends on the matrix where cannabinoids need to be extracted from, and contributes to the success of subsequent analytical methods for the analysis of cannabinoids. This talk will provide a critical overview of the literature published during the last decade on the use of various extraction methods for the extraction of naturally occurring cannabinoids from various matrices.

Speaker: Prof. Satyajit Sarker (John Moores University, Liverpool)

Friday, 21 January

Keynote Lecture: Session 3

Conveners: Animesh Ghosh (Birla Institute of Technology, Mesra) , Sandeep Kumar Singh (Birla Institute of Technology, Mesra)

6 Assessment of drug-drug interaction in pediatric drug development: Application of physiology-based pharmacokinetic modeling

Assessment of pharmacokinetic (PK) drug-drug interaction (DDI) is an important requirement of drug development. This is necessary because characterizing the clinically relevant DDIs inform the dose adjustment strategy in patients receiving polypharmacy. However, typical drug development trials are restricted to adult population only (i.e., excluding children) due to ethical and logistical constraints. This leaves the pediatric population as ‘therapeutically orphan’, because the safe and effective dosage for this population are not formally determined during typical drug development. As a result, drug dosing in the pediatric clinics are largely off-label, which impose significant risk to this special population. In addition to this, presence of DDIs further increase the risk.
Unlike adults, dedicated DDI studies are rare in children, primarily because, most clinical pharmacology studies in pediatric patients are done opportunistically. Therefore, assessment of DDI in children becomes challenging using the conventional methods used in adults. Physiology-based pharmacokinetic (PBPK) modeling, in this context, is useful to address the gap. PBPK modeling has the unique ability to predict the PK of a drug by integrating the drug-specific properties with the physiological variables of the target population, obviating the need of extensive clinical data. Therefore, application of PBPK modeling is increasing in understanding the possible DDI implications in pediatric dose adjustment.
This work demonstrates the use of PBPK modeling in understanding the DDI potential of enzyme-inducing antiepileptic drugs (EIAEDs) on the PK of oxcarbazepine and levetiracetam, two new generation antiepileptic drugs (AEDs), frequently used in pediatric epileptic patients.

Speaker: Dr Jaydeep Sinha (University of North Carolina at Chapel Hill)

7 Computer-aided drug discovery: From small compounds to protein inhibitors against tyrosine kinase of EGFR for cancer therapy

Computational studies are an essential part of research in Biochemistry today. The goal of theoretical investigation of biochemical processes is to gain a deeper insight into the molecular mechanism behind the process of study. It can further be used to predict the results of experiments. Protein Bioinformatics is a useful technique to understand biochemical processes of proteins on various levels including protein modeling, protein docking, and protein molecular dynamics. In our group, we focus on the anticancer targeted protein, the epidermal growth factor receptor (EGFR). This protein plays a crucial role in cellular signaling pathways that regulates key functions, especially proliferation. The EGFR abnormalities have been associated with several types of human cancer. Nowadays, there are cancer-treated drugs that inhibit the activity of tyrosine kinase (TK) domain of EGFR – a signaling part of this protein. However, each drug specifically treats with each cancer type and some tumor patients have resisted to those drugs. A discovery of better new efficient inhibitors is extremely needed. The virtual screening of medicinal plant compound databases against EGFR-TK have been used to discover new inhibitors. These compounds were tested on enzymatic inhibiting assay and non-small cell lung cancer cells, A549.

Speaker: Dr Kiattawee Choowongkomon (Kasetsart University, Bangkok)

10:30 Tea Break

8 Nanotechnology in healthcare: Are we in the right direction?

Nanotechnology is revolutionizing global industrial output and pharmaceutical industry is showing immense interest in nanoproducts owing to the emerging era of infectious diseases. The global nanotechnology healthcare market is expected to grow at a CAGR of around 11.9% in the period ranging from 2020 to 2026 and is estimated to reach USD 461, 252 million by 2026. The sole share of this segment will ensure a technological leap in the future of pharmaceutical R&D sector. The ongoing pandemic has showed us the grave intensity of how vicious an infectious disease can get if arrived unannounced. The level of socio-economic impact that is being witnessed due to the Covid-19 pandemic is beyond imagination and forces us to think towards the development of versatile platforms that can help combat any such unknown disease in the future. This implies not only to the therapeutic platforms but also towards the diagnostic and prophylactic areas. Considering the importance and need of research in these areas, we at VBP Research Group have put our best foot forward and have developed technologies encompassing novel nanotechnology-based strategies pertaining to the diagnosis, prophylaxis as well as therapy of infectious diseases. The presentation will comprise a discussion of the case studies pertaining to the diagnosis of Brucellosis and further development of a green nanotechnology-based vaccine, both being award-winning patented ideas. Our patented antimalarial platform based on nanostructured lipid carriers (NLCs) will be discussed in depth. The presentation will give an overview of the need for research in nanotechnology in the healthcare sector in today’s times and will pave way for a generation of many new ideas to take this research in the right direction.

Speaker: Prof. Vandana B Patravale (Institute of Chemical Technology, Mumbai)

9 Exploring the biosafety profile of novel biopoymeric nanoparticles in drug targeting

Biomaterials can be considered safe, but at nano size even a biomaterial can pose serious toxic issues to humans as well as a threat to the environment when compared to their macro or micro-sized counterparts. In humans, due to small size of nanocarriers, they can easily cross biological membrane and long exposure leads to their accumulation in cells, tissues and blood. Nanocarriers have unique surface chemistry and a huge surface area. Their highly reactive surface acts as a catalyst in the formation of reactive oxygen species (ROS), which in turn causes the generation of increased oxidative stress leading to lipid peroxidation, mitochondrial and DNA damage and ultimate cell death. Thus it is essential to establish the safety profile of a nanoformulation before it can be a part of the biomedical application. So, cytotoxicity and hemocompatibility of blank novel lignin nanoparticles were studied to ascertain the safety of lignin nanoparticles and the Drosophila melanogaster model was used to study the possible genotoxicity of blank nanoparticles causing behavioural and phenotypical alterations. After establishing the safety profile of optimized blank lignin nanoparticles (BLNPs), exhaustive blood compatibility studies on BLNPs, were carried out as these particles were designed for the intravenous administration.

Speaker: Dr Sushama Talegaonkar (Delhi Pharmaceutical Sciences and Research University, New Delhi)

12:45 Lunch Break

Oral Presentations: Session 4

Oral presentation by a registered participant, selected through a peer-review process

Conveners: Manik Ghosh (Birla Institute of Technology, Mesra) , Sandeep Kumar Singh (Birla Institute of Technology, Mesra)

10 Microemulgel containing Nigella sativa oil and berberry extract for treatment of hypo pigmentation.

Formulate and evaluate microemulgel for skin pigmentation, containing a combination of Nigella sativa oil and Berberry extract. Nigella sativa oil is rich in thymoquinone, and berberry extract contains berberine. The solubility studies of nigella oil and berberry extract were conducted to select surfactants and cosurfactant. The pseudo ternary phase diagram was constructed based on the chosen oil and combination of surfactant and co-surfactant (Tween80 and propyleneglycol 400) at different ratios (1:1, 2:1, 3:1, 4:1, 5:1, 6:1). The microemulsion was assessed for globule size, zeta potential, pH value. The microemulsion was incorporated into a 1% carbopol 934 gel base and evaluated for spreadability, viscosity, drug release, drug content, and tyrosinase activity. The stability study of the optimized formulation was carried out as per ICH guidelines. A zero-order drug release mechanism was exhibited by microemulgel. The optimized microemulgel showed good stability for three months at accelerated conditions. The average globule size was 185.5 nm, the zeta potential was 0.4 mV, and drug permeation was 90.22% and 88.62% for berberine and thymoquinone, respectively, within 24 h. The tyrosinase activity results showed that a combination of berberry extract and Nigella sativa oil act as a tyrosinase accelerator. The optimized microemulgel formulation containing Nigella sativa oil and berberry extract is a stable and promising skin darkening agent.

Speaker: Ms Pranali Badhe (Shri D D Vispute College of Pharmacy and Research Center, Panvel)

Microemulgel containing Nigella sativa oil and Berberry extract for treatment of hypo pigmentation

11 Pharmacognostical and phytochemical screening on leaves of Ipomoea sagittifolia Burm. F

The drug evaluation and bioassay of traditional herbs of various herbal systems are now getting more momentum throughout the world. The present study provides information in respect of their identification, standardization of herbal drugs of the folk medicinal practice of present, and enrichment of Ayurvedic Pharmacopoeia. It is high time now to evaluate scientifically the information stored in different herbal medicine systems of the world in terms of their pharmacognostic and phytochemical characterization. So knowledge of the pharmacognosy of individual medicinal plants is a very important aspect for herbal-based drug discovery. Therefore in this study, an attempt has been made to evaluate such ethnomedicinally important plant, pharmacognostical and phytochemical analyses which are still unexplored. In this study, different pharmacognostical parameters of Ipomoea sagittifolia Burm.f. belonging to the family of Convolvulaceae, an ethnobotanically important medicinal plant, has been investigated. WHO recommended physico-chemical determinations and authentic phytochemical procedures. The physicochemical, morphological, and histological parameters presented in this paper may be proposed as parameters to establish the authenticity of the leaf of I. sagittifolia and may possibly help to differentiate the drug from its other species. In the leaf extract, the detected phytochemical groups are alkaloids, flavonoids, steroids, and triterpenoids, reducing sugars, tannins, gums, and saponins, etc. This study will be beneficial to herbalists and pharmacognostical and phytochemical for proper evaluation and validation of folk drugs. Herbal drugs used in various traditional medicine need detailed investigation with an ethnopharmacological approach.

Speaker: Mr Muthulakshmi R (Periyar College of Pharmaceutical Sciences, Tiruchirappalli)

Pharmacognostical and Phytochemical Screening on Leaves of Ipomoea sagittifolia Burm.Fil.

12 Development of a polyherbal formulation in the management of osteoporosis in post menopausal women

Osteoporosis affects all women, and osteoporotic fractures are more common in menopausal women, which accounts for significant morbidity and mortality. Certain herbs have potential effects in promoting gonadal function, fracture healing and are suitable to counteract/ prevent postmenopausal osteoporosis as compared to synthetic drugs that have been reported for their side effects, including hypercalcemia, vaginal bleeding, risk of endometrial and breast cancer. In the current research, the herbal drugs that have been claimed to improve bone mineral density, lower menopause symptoms, and recommended as an herbal tonic for osteoporosis in women were selected and formulated as capsules. The poly herbal formulation (PHF) containing the alcoholic extracts of Meremmiaumbellata (Convulvulaceae), Hydrocotylejavanica (Apiaceae), and Peristrophebicalyculata (Acanthaceae) was developed and screened for anti-osteoporosis activity in experimental rat models. Results obtained in the present study indicated that treatment with PHF (500 mg/kg) showed a significant increase in femur length, femur diameter, restoration of serum calcium and alkaline phosphate levels, improvement in body weight as compared to positive control rats. Femur bone weight and density were significantly restored with improvement in bone breaking strength after the treatment of PHF. Histopathological study of the femur bone further supported the antiosteoporotic activity. These results showed that developed Poly Herbal Formulation showed significant protection against ovariectomy-induced osteoporosis in rats. Our present investigation supports the use of the developed polyherbal formulation in the treatment of osteoporosis, especially in post-menopausal women.

Speaker: Dr Shri Vijaya Kirubha T (Periyar College of Pharmaceutical Sciences, Tiruchirappalli )

Development of a Polyherbal Formulation in the management of Osteoporosis in post menopausal women

13 HPTLC method development for simultaneous estimation of Andrographolide, Gallic acid and Quercetin from herbal extracts with implementation of Quality by Design (QbD)

Development of Quality by Design (QbD) based sensitive, economic and robust high performance thin layer chromatographic (HPTLC) method for simultaneous estimation of Andrographolide (A), Gallic acid (G) and Quercetin (Q) in herbal extracts. The chromatographic separation was carried on Merck TLC aluminum sheets of silica gel 60 F254 (20 × 10 cm) with a mobile phase of toluene: ethyl acetate: methanol: formic acid (4:3:1:0.05) with densitometric scanning at 232 and 256 nm. QbD approach was implemented by investigating Critical Method Parameters (CMPs) through regular two-level factorial design by using a trial version of Design Expert-13 software and evaluated for their effect on selected critical analytical attributes that are retention factor (R$_{f}$) and peak area. The Pareto charts, 3D response surface plots, and contour plots (Figure 1) for the constructed model demonstrated a significant influence of the selected factors on responses of A, G, and Q. The results obtained using the regular two-level factorial design for screening of CMPs indicated that the composition of the mobile phase ratio had a significant effect on the retention factors and areas of A, G, and Q. The method parameter of saturation time and wavelength had a minor effect on the R$_{f}$ values, while the wavelength had a significant effect on all areas. Under the optimized conditions, the biomarkers were suitably resolved with R$_{f}$ values of 0.38±0.02, 0.24±0.02, and 0.50±0.02 for A, G, and Q, respectively, with the linearity in the concentration range of 400- 2400 ng/band for A, 200-1200 ng/band for G and Q, high accuracy of 98.9-99.8%, and intra- and interday precision of %RSD <2%. This validated HPTLC method developed through a QbD approach was successfully employed for quantification of A, G, and Q in selected herbal extracts. The optimized method was proved to be economical, robust, time-saving and thus, can be used for simultaneous estimation of A, G, and Q in other herbal extracts and herbal formulations.

Bibliography:

1. Kumar N, Sangeetha D. (2020) Analytical method development by using QbD-An emerging approach for robust analytical method development. J Pharm Sci Res 12(10):1298-1305.

Speaker: Ms Monika Jadhav (C U Shah College of Pharmacy, Mumbai )

HPTLC method development for simultaneous estimation of Andrographolide, Gallic acid and Quercetin from herbal extracts with implementation of Quality by Design (QbD)

14 Simultaneous estimation of antihypertensive agents by two different UV methods

The aim of this study is to develop and validate two analytical methods for the simultaneous estimation of Amlodipine besylate (AMLO) and Hydrochlorothiazide (HCTZ) using simultaneous equations method and absorption ratio method by UV spectrophotometry. Method A involved the simultaneous equations method. The two wavelengths, 238 nm (λ$_{max}$ of AMLO) and 271 nm (λ$_{max}$ of HCTZ), were chosen for the formation of simultaneous equations method. Beer Lambert’s law was obeyed in the concentration range of 5-35 μg/mL for amlodipine besylate and hydrochlorothiazide, respectively with a correlation coefficient (r$^{2}$) greater than 0.990. For Q absorbance ratio method, 253 nm (isosbestic point) and 271 nm (λ$_{max}$ of HCTZ) were chosen as the two wavelengths for analysis. A concentration range of 5-35 μg/mL for AMLO and HCTZ, respectively, with a correlation coefficient (r$^{2}$) greater than 0.990, was selected as per beer’s law. The developed method validation was done as per ICH guidelines. The % assay of AMLO and HCTZ were found to be 99.670 % and 101.086% by simultaneous equations method and 98.038% for amlodipine and 100.230% by absorption ratio method, which were within the acceptable limit. The developed methods were simple, sensitive, accurate, precise, and robust and can be used for the simultaneous estimation of the two drugs in tablet formulation.

Bibliography:

1. Safeer K, Anbarasi B, Senthilkumar N. (2010) Analytical method development and validation of amlodipine and hydrochlorothiazide in combined dosage form by RP-HPLC. Int J ChemTech Res 2(1):21-5.

2. Vyankatrao GD, Omprakash B, Anil KA. (2015) Method development and validation of amlodipine besylate and hydrochlorothiazide in their bulk and combined dosage form. Der Pharm Lett 7:220-224.

3. Patel G, Patel S, Prajapiti D, Mehta R. (2010). RP-HPLC method for simultaneous estimation of amlodipine besylate and hydrochlorothiazide in combined dosage forms. Stamford J Pharm Sci 3(1):49-53. DOI: https://doi.org/10.3329/sjps.v3i1.6798

Speaker: Leena Sawaikar (PESs Rajaram and Tarabai Bandekar College of Pharmacy, Goa)

Simultaneous estimation of antihypertensive agents by two different UV Methods

15 Significance of physico-chemical and bacteriological parameters in summation of water quality in KIET, Ghaziabad

Water quality is a vital concern for humanity as it is directly linked with human welfare. A parameter selection for determining water quality is totally based on the purpose of its use and the extent of required water quality and purity. With this knowledge, this paper deals with the study on analyzing drinking water parameters in a reputed educational institute situated in Muradnagar, i.e., KIET, Ghaziabad. Monthly changes in physical and chemical, and bacteriological parameters such as water temperature, turbidity, total dissolved solids, pH, dissolved oxygen, carbonate, bicarbonate, total alkalinity, hardness, calcium, magnesium, chloride,su, etc. were analyzed for a period of one year from July 2020 to June 2021. The sampling frequency was once a month. Various physicochemical parameters were selected for assessment (pH, temperature, color, odor, turbidity, total hardness, total dissolved solids, total suspended solids, chloride, fluorides, nitrates, lead, and arsenic). Moreover, the bacteriological study was recorded by finding entire coliform colonies. The results obtained were compared with WHO and EPA standards for drinking and recreational water. Except for drinking water of some floors of boys hostel that do not comply with chloride and pH standards, respectively, all other parameters were in the standard range. The present review paper depicts the importance of various parameters in reckoning water quality to check its suitability for drinking, industrial, or marine life, etc.

Speaker: Prarthana Srivastava (K I E T Group of Institutions, Ghaziabad)

Significance of physico-chemical and bacteriological parameters in summation of water quality in KIET ,GHAZIABAD

16 Development of novel synthetic methodologies from aryl ketones and its application in API’s synthesis

There has been a very high demand for API intermediates to synthesize drugs in recent years. Carbonyl functionality is an essential precursor for drugs and their intermediates synthesis in the pharmaceutical industry. Most widely used carbonyl groups to prepare carboxylic acid, ester, aldehyde, ketones, amine, and amide APIs. We choose carbonyl ketones as a critical starting material for the synthesis of API’s Intermediate because of its stability, cheapness, ease of handling, and wide applications in pharmaceutical industries such as an excipient, reaction solvents, synthetic fiber, and medicines. We have developed simple, efficient synthetic routes for the critical heterocyclic nucleus such as 2-aminothiazole, 2-phenyl pyridine, and α-N-heteroaryl ketone. Representative drugs which contain 2-aminothiazole are meloxicam (NSAID), 2-phenyl pyridine is etoricoxib (COX Inhibitor), and α-Nheteroaryl ketone is econazole (azole antifungal). In 2020, these drugs will be commonly prescribed medication in the United States, with more than 34 million prescriptions. Results of the following invented methodologies will be presented, with their pharmaceutical applications in drug synthesis of

1. 2-aminothiazole from aryl ketone

2. 2-aryl pyridine from aryl ketones

3. α-N-heteroaryl ketone from aryl ketone

Bibliography:

1. Ghodse SM, Telvekar VN. (2015) Synthesis of 2-aminothiazole derivatives from easily available thiourea and alkyl/aryl ketones using aqueous NaICl2. Tetrahedron Lett 56(2):472-474. DOI: https://doi.org/10.1016/j.tetlet.2014.11.140

2. Ghodse SM, Telvekar VN. (2017) Synthesis of 2-phenyl pyridine derivatives from aryl ketones and 1, 3-diaminopropane using palladium acetate as a catalyst. Tetrahedron Lett 58(6):524-526. DOI: https://doi.org/10.1016/j.tetlet.2016.12.075

3. Ghodse SM, Hatvate NT, Telvekar VN. (2021) One pot synthesis of α‐N‐heteroaryl ketone derivatives from aryl ketones using aqueous NaICl2. J Heterocycl Chem 1. DOI: https://doi.org/10.1002/jhet.4412

Speaker: Shrikant Ghodse (Principal K M Kundnani College of Pharmacy, Mumbai)

91_DEVELOPMENT OF NOVEL SYNTHETIC METHODOLOGIES FROM ARYL KETONES AND ITS APPLICATION IN API’s SYNTHESIS

17 Design, synthesis and evaluation of the cholinesterase inhibitory potential of 5-chlorobenzimidazole derivatives for Alzheimer’s

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder leading to a decline in cognitive function and behavior. It is characterized by depletion in acetylcholine and butyrylcholine, presence of amyloid deposits, formation of neurofibrillary tangles in the brain. Donepezil, an acetylcholinesterase inhibitor remains the leading compound for symptomatic relief of AD patients. Thus, cholinesterase is a promising target to explore the therapeutic effect for AD. By blocking AChE peripheral anionic site, its co-localization with amyloid fibrils can be restricted and hence limiting plaques deposition in different regions of the brain. Extending study towards the development of cholinesterase inhibitors may eventually prevent precipitation of amyloid plaques and neurofibrillary tangles hence justifying its targeted interest. Nitrogen-containing heterocyclic scaffolds are known to possess potential activity towards AD targets. Hence, we intend to explore the therapeutic effect of substituted 5-chlorobenzimidazole derivatives as potential acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors with their neuroprotective role. Ligands were sketched and minimized with LigPrep under the force field of OPLS-2005 (Schrödinger’s Maestro release 2018-1). QikProp v.5.5 (Schrödinger’s Maestro release 2018-1) was accessed for in-silco ADME. 5-chlorobenzimidazole derivatives were synthesized with benign synthetic methods. The purified derivatives were characterized by infrared spectroscopy (IR) and proton nuclear magnetic resonance ($^{1}$HNMR). The masses of the target compounds were confirmed through LC-MS (ESI). In-vitro LPO (lipid peroxidation) assay was performed on rat brain. Cholinesterase inhibition was carried out on the synthesized derivatives using Ellman’s method. All the derivatives exhibited favourable drug like properties and the results were complying with the QikProp recommended range. In-vitro LPO assay results were in the range from 2.80 – 31.68 μM depicting their neuroprotective potential with Bz–6 being the most effective. In-vitro cholinesterase inhibition assay indicated that BZ series potentially inhibited BuChE over AChE. Substituted Bz-10 with IC$_{50}$ 4.25 mM was the most potent BuChE inhibitor. 5-chlorobenzimidazole derivatives showed favourable ADME parameters, portraying neuroprotection and cholinesterase inhibition. Cholinesterase inhibition was found to be more promising against BuChE as compared to AChE at 10 µM. Hence, these can act as effective candidates for symptomatic treatment of AD.

Speaker: Ms Sonal Pathak (Principal K M Kundnani College of Pharmacy, Mumbai)

Design, synthesis, and evaluation of the cholinesterase inhibitory potential of 5-Chloro Benzimidazole derivatives for Alzheimer’s

18 Design, development, and evaluation of pyrazoline based mycobactin analogues as anti-tubercular agents: An in-silico approach

As evidenced by the WHO database, the pathogenicity and virulence of Mycobacterium tuberculosis have increased its infectiousness, making it a fatal disease causing a global health crisis. One of the vital health aims of the United Nations Sustainable Development Goals is to eradicate tuberculosis by 2030. The rise in multidrug-resistant tuberculosis (MDR-TB)/ drug-resistant tuberculosis (XDRTB) cases has pushed scientists to create new chemotherapeutic agents with distinct mechanisms of action as the current medications seem to be ineffective to some extent. In this perspective, we have employed the concept of “conditionally essential target” (CET) based drug design because, over the years, mycobacteria have evolved machinery by which they can survive in the host. Therefore, it is of utmost importance to target specific enzymatic machinery that seems essential for mycobacteria’s survival. As per the current review by our research group (Shyam et al. 2021), the mycobactin biosynthesis pathway (MBP) might be a prospective therapeutic target in combating tuberculosis. Mycobacteria take up mycobactins (siderophores/iron chelators) when they face iron-deficient conditions, i.e., up-regulation of the MBP. This makes MBP a promising endogenous target for identifying new lead molecules. Therefore, we aim to design and develop mycobactin-mimicking compounds by retaining the structural features of mycobacterial siderophores in anticipation that it might cause inhibition of the siderophores biosynthesis enzymes resulting in the arrest of bacterial growth under iron deprived conditions. Herein, we focus on exploring pyrazoline based mycobactin analogues (non-specific mycobactin biosynthesis inhibitors) targeting MbtA enzyme (1st step of mycobactin biosynthesis). Following our prior studies described by (Stirrett et al. 2008) and (Ferreras et al. 2011), we now wish to look into the structural diversity of the previously found active compounds with a hope of finding a more potent analogue showing high affinity for MbtA (adenylating enzyme) in the in-silico exercise. Hence, we designed a small library (12 molecules) of mycobactin analogues keeping the necessary scaffold (diaryl-substituted pyrazoline (DAP)) intact and assessed their in-silico stability using molecular docking simulations (AutoDock 4.2.6) and molecular dynamics simulations (GROMACS). To find the binding modalities and inhibitory profile of the proposed compounds, they were docked in the active site of the MbtA receptor (by analogy with the homologous structure PDB ID: 1MDB). The lowest energy conformation of each docked ligand (best score) was visualized in BIOVIA discovery studio. The six top-scoring compounds were evaluated for their ADMET (absorption-distribution metabolism-excretion-toxicity) profile using SwissADME and pkCSM web server. The best molecule which revealed a good ADMET profile was taken up for MD simulation study (50 ns). Results revealed that the designed compound GV08 (-8.80, 352.58 nM), GV09 (-8.61, 499.91 nM), GV03 (-8.59, 508.51 nM), GV07, (-8.54, 553.44 nM), GV02 (-8.53, 563.30 nM), and GV04 (-8.26, 878.26 nM) had good docking score and inhibition constant. Of these GV08 and GV09 showed a good ADME profile with all major parameters lying in the acceptable ranges. They also showed the least toxicity with no hepatotoxicity and skin sensitization. MD simulation studies of GV08 also suggest that the protein-ligand complex is stable throughout the simulation. The future scope invalidates these findings through synthesis, characterization, and intracellular activity.

Bibliography:

1. Shyam M, Shilkar D, Verma H, Dev A, Sinha BN, Brucoli F, Bhakta S, Jayaprakash V. (2021) The Mycobactin Biosynthesis Pathway : A Prospective Therapeutic Target in the Battle against Tuberculosis. J Med Chem 64:71–10. DOI: https://doi.org/10.1021/acs.jmedchem.0c01176

2. Stirrett KL, Ferreras JA, Jayaprakash V, Sinha BN, Ren T, Quadri LE. (2008) Small molecules with structural similarities to siderophores as novel antimicrobials against Mycobacterium tuberculosis and Yersinia pestis. Bioorganic Med Chem Lett 18:2662–2668. DOI: https://doi.org/10.1016/j.bmcl.2008.03.025

3. Ferreras JA, Gupta A, Amin ND, Basu A, Sinha BN, Worgall S, Jayaprakash V, Quadri LE. (2011) Chemical scaffolds with structural similarities to siderophores of nonribosomal peptide–polyketide origin as novel antimicrobials against Mycobacterium tuberculosis and Yersinia pestis. Bioorg Med Chem Lett 21:6533–653. DOI: https://doi.org/10.1016/j.bmcl.2011.08.052

Speaker: Mr Gourav Rakshit (Birla Institute of Technology, Mesra)

Design, development, and evaluation of pyrazoline based mycobactin analogues as anti-tubercular agents: An insilico approach

19 Memory enhancing effects of citrullus seed oil in mice are correlated with antioxidant protection and acetylcholinesterase inhibition

Brain aging is characterized by cognitive decline and memory deficits that could be the result of oxidative stress and impaired cholinergic function. Several recent studies have suggested that higher intake and blood levels of omega-3 fatty acids may help to reduce the risk of age-related cognitive decline, dementia, and Alzheimer’s disease. The major dietary sources of these fatty acids are fish and shellfish from both salt water and fresh water. EPA and DHA can also be synthesized from the elongation and desaturation of alpha-linolenic acid, which is present in some vegetable oils. Oxidative stress significantly contributes to neuronal damage seen in cases of cognitive impairment and Alzheimer’s disease by depleting the brain of vulnerable, highly unsaturated fatty acids (e.g., EPA and DHA). Some researchers suggest that by replenishing brain cells with EPA and DHA via higher intake levels, individuals may help protect themselves against cognitive decline to a significant degree. These findings prompted us to investigate the effects of daily, 7-day, oral administration of Citrullus vulgaris seed oil on learning and memory by interoceptive behavioral models (passive avoidance test and elevated plus maze), their brain AChE activity, and oxidative status. Whole-brain homogenates were collected for examination of brain oxidative markers and acetylcholinesterase (AChE) activity. Results showed that the short-term supplementation of both healthy adult and aged mice significantly exhibited improvement in learning and memory in the passive avoidance test and attenuated brain oxidative stress markers. Furthermore, AChE activity was significantly decreased only in adult mice. Thus, we showed, for the first time, the significant cognitive enhancement conferred by C. vulgaris seed oil administration in mice is more closely related to antioxidant reinforcement.

Speaker: Rahul Adnaik (Anandi Pharmacy College, Kolhapur)

Oral Presentation at International Conference ICETD3-2022

20 Potential TLR-4/MD-2 complex antagonism initiated bacterial asthma exacerbation treatment

To optimize the animal model of asthma through TLR4 receptor antagonism mechanism as bacterial infections frequently cause asthma exacerbation. TLR4 responds to bacterial stimulation, putting toll-like receptors (TLRs) at the frontline of our microbial defense. This study showed how TLR4 stimulation and TLR4/MD2 complex inhibition were utilized for AHR allergic asthma management in a mouse model. Swiss albino mice were induced with the administration of PBS, LPS, and ovalbumin; later, two compounds activated the TLR4 receptor underlying mechanism for asthma induction. It was 23 days protocol in which animals were sensitized (i.p). It challenged intranasally (i.n.) and treatment given on the 21$^{st}$ & 22$^{nd}$ day followed by euthanasia and samples (BALF & lungs tissues) collected on day 23$^{rd}$. Further analysis such as TLC/DLC & lung histopathology of asthma parameters in toxic & treatment groups compared to the standard group was performed. Bronchial smooth muscle hyperplasia and goblet cells swelling developed in poisonous groups. The bronchoalveolar lavage fluid (BALF) analysis demonstrated a significant increase in inflammatory infiltration and bronchial architectural damage. In contrast, bovine serum albumin delivery causes allergic airway irritation. The bacterial asthma exacerbation caused by LPS drug rise was decreased by treatment with a TLR4/MD2 complex inhibitor, which significantly reduced cell inflow in BALF. The airway-stabilizing action of TLR4 antagonist drugs suggests that TLR4-MD2 problematic inhibitor drug shown positive therapeutic potential compared to standard medications and could be used to treat microbial-induced allergic asthma exacerbations in the future.

Speaker: Ms Swamita Arora (Amity Institute of Pharmacy, Noida)

Potential TLR-4/MD-2 complex antagonism initiated bacterial asthma exacerbation treatment

21 Evaluation of in-vitro and in-vivo anti-asthmatic activity of curcumin and vasicine

Asthma is a condition in which a person’s airways become inflamed, narrow, and swell and produce extra mucus, which makes it difficult to breathe. Asthma can be minor or in some cases, it may lead to a life-threatening attack. Curcumin (Curcuma longa) and Vasicine (Adathoda vasica) are traditional Indian medicine used in the treatment of bronchial asthma. They have various pharmacological activities such as anti-inflammatory, bronchodilator and antioxidant. The aim of this study is to evaluate the in-vitro and in-vivo activity of curcumin and vasicine against airway inflammation. In in-vitro histamine-induced contraction on isolated guinea pig tracheal chain preparation method, the guinea pig tracheal chain is prepared and initial responses were recorded with histamine. After giving wash, responses were recorded in presence of a single constituent (curcumin 100 µg/mL and vasicine 30 µg/mL) and combination. In in-vivo ovalbumin (OVA) induced allergic airway inflammation mouse model, the animals were sensitized and challenged by Ovalbumin/ AloH. The BALB/c mice were administrated orally with curcumin(100 mg/kg) and vasicine (3mg/kg) alone and in combination, total and differential count in BALF and IgE level in serum was counted using ELISA. Contraction produced by histamine was antagonized and produced relaxation by the combination of curcumin and vasicine than single constituent. Treatment of mice with the curcumin and vasicine combination reduces the total and differential count of bronchoalveolar lavage fluid (BALF)(p<0.001) and IgE serum level in the mice(p<0.001) when compared with curcumin and vasicine alone treated groups(p<0.01). The data indicate that the combination of drugs produces relaxation of smooth muscle, reduced the total and differential count and IgE, level in serum. Therefore this study revealed that curcumin and vasicine combination shows a synergetic effect on the inhibition of inflammatory mediators which is useful to treat asthma. From the result, it was concluded that curcumin and vasicine may be an alternative for the conventional drug against asthma.

Speaker: Ms Shila G (Nandha College of Pharmacy, Erode )

Evaluation of in-vitro and in-vivo anti-asthmatic activity of Curcumin and Vasicine

22 Formulation and evaluation of orodispersible tablets of Trimethobenzamide HCl

Orodispersible drug delivery system has shown bioavailability of drug significantly greater than conventional drug delivery system and dissolves rapidly in saliva without the need of water. Trimethobenzamide HCl is an anti-emetic drug and acts within the central nervous system to inhibit the medullary chemoreceptor trigger zone by blocking emetic impulses (dopaminergic) to the vomiting center. The present research work was an attempt to develop orodispersible tablets of Trimethobenzamide HCl with the aim of rapid therapeutic effect with good mouth feel and to enhance patient compliance. The preformulation studies included FTIR, and DSC of the drug was carried out to study the behavior of the drug. The drug excipient compatibility showed no significant interaction between drug and excipients used in the formulation. The tablets were formulated by wet granulation method using Crosspovidone as a super disintegrant and Poly vinyl pyrrolidine as a binder to provide faster disintegration and drug release. 32 full factorial design was performed to study the effect of the formulation variables (Crosspovidone and Mannitol) on disintegration time. Tablets were evaluated for their morphology, micromeritics properties, drug content, wetting time, water absorption ratio, disintegration time, and dissolution studies. Numerical optimization was performed to find the optimum composition, and based on this; an optimized formulation was selected. Optimization studies showed that the extra design check point formulation (F10) matched closely with optimized formulation (F3) with a similarity factor of 96.89%. Kinetic studies for in vitro drug release followed Korsmeyer’s–pepp as a model. Disintegration time of optimized formulation was found to be 26 sec with 99.51% of drug release within 15 min. Finally, it was concluded that the developed orodispersible tablets for Trimethobenzamide HCl could be a promising system for rapid action, good mouth feel as well as better patient compliance.

Speaker: Sakshi Garg (K I E T School of Pharmacy, Ghaziabad)

23 Synthesis of green nanofiber mat for tissue engineering applications

Tissue engineering is the discipline that deals with the regeneration of damaged tissues. Nanofibers are the most acceptable substances for the regeneration of tissues because it mimics the extracellular cellular matrix (ECM), so the cells can quickly proliferate on it. Natural polysaccharides are used to develop nanofibers because of their biocompatibility and biodegradability. But certain limitations are also associated with these natural polysaccharides, such as low mechanical property, so chemically derived polymers are also incorporated with the natural polysaccharides to overcome this limitation. Nanofibers can be procured using various techniques; electrospinning is the most favored technique. This perspective aims to explore the combination of polyvinyl alcohol (PVA) and neem gum (NG) to fabricate nanofibers using the electrospinning technique. Various nanofibers were prepared by varying the concentration of PVA and NG. The preparation of nanofibers was confirmed using multiple analytical methods. The antimicrobial activity of PVA, NG, and PVA/NG nanofiber was investigated against bacteria such as Staphylococcus aureus and Escherichia coli using the disk diffusion method. Nutrient agar media was used for the incubation of bacteria. The NG and PVA/NG nanofiber can inhibit the growth of bacteria. This suggests that the nanofiber will provide a framework for the proliferation of cells and can treat the infections caused by bacteria.

Speaker: Aditya Dev Rajora (Birla Institute of Technology, Mesra)

Synthesis of Green Nanofiber Mat for Tissue Engineering Applications

24 Development and characterization of geniste in nano structured lipid carriers loaded topical nanogel to target melanoma cells

The aim of the present study was to develop topical nanogel utilizing genistein loaded nanostructured lipid carriers (GEN-NLCs) in order to provide a controlled release and targeting skin epidermis. The different batches of GEN-NLCs were prepared by solvent diffusion method using orthogonal Taguchi optimization design. Then, GEN-NLCs were evaluated for various physicochemical parameters like particle size, zeta potential, entrapment efficiency, and in-vitro drug release studies. Morphological studies were performed using scanning electron microscopy and atomic force microscopy. Moreover, in-vitro anticancer studies and cellular uptake studies by fluorescence microscopic studies were performed on A-375 melanoma cell lines. GEN-NLCs loaded gels were prepared utilizing methocel and characterized for particle size and texture profile analysis (TPA). Further, the optimized gel was evaluated for in-vitro and ex-vivo occlusion test, in-vitro release study, ex-vivo human skin permeation & retention study. GEN-NLCs were found to be in the nanometric range with 89.50% entrapment efficiency and -14.98 mV zeta potential. Release studies confirmed the controlled release nature of the NLCs. In-vitro anticancer activity by MTT assay revealed that the nanoparticles were found to be 15.37 times more effective against melanoma as compared to the drug, whereas fluorescence studies confirmed enhanced cellular uptake with time. The results of the evaluation of gel indicated that there is no significant change in the texture profile of hydrogel after incorporating GEN-NLCs having 3% of methocel gel. GEN-NLCs loaded gels showed an occlusion factor almost 3.45 times higher than control gel at the end of 24 h resulting in a significant increase in the occlusivity of the hydrogel. In-vitro release kinetic data of Genistein exhibited the sustained release of drug which follows Higuchi release kinetics ex-vivo studies further confirmed a decrease in flux across the skin, i.e., controlled release pattern of GEN from hydrogel and increased hydration and retention in the epidermis. Topical delivery of GEN-NLCs loaded gel showed a potential delivery system to target skin epidermis for melanoma cancer.

Speaker: Dr Lakshmi . (K I E T School of Pharmacy, Ghaziabad)

Development and Characterization of Genistein Nanostructured Lipid Carriers Loaded Topical Nanogel to Target Melanoma Cells

Poster Presentations: Session 5

Poster presentation by a registered participant, selected through a peer-review process

Conveners: Animesh Ghosh (Birla Institute of Technology, Mesra) , Ashok Kumar Patnaik (Birla Institute of Technology, Mesra)

25 Evaluation of antidiarrheal activity of ethanolic leaf extract of Phyllanthus amarus S. in wistar albino rats

Diarrhea is defined as the passage of more watery stools three or more times per day. It is the second leading cause of death in children under five years of old. Loperamide and other antibacterial drugs are usually preferred for treating diarrhea. Loperamide may cause addiction and cardiotoxicity. Phyllanthus amarus S. is traditionally used in treating many health problems such as jaundice, urinary bladder disturbances, wound healing, skin ulcer, etc. The aim of this study is to evaluate the antidiarrheal activity of ethanolic leaf extract of Phyllanthus amarus S. (EEPA). The preliminary phytochemical screening of Phyllanthus amarus S. was performed. The antidiarrheal activity is evaluated for EEPA with doses 250 mg/kg and 500 mg/kg. The models used to assess the antidiarrheal activity include charcoal meal test, castor-oil induced diarrhea, castor-oil enteropooling, and magnesium sulfate-induced diarrhea. The phytochemical screening confirmed the presence of saponins, tannins, triterpenoids, steroids, flavonoids, alkaloids, proteins, and carbohydrates in EEPA. In the charcoal meal test, the EEPA suppressed the propulsion of charcoal meals by reducing gastrointestinal motility (p<0.01). In castor oil-induced diarrhea, the EEPA treated animals showed a significant decrease in water and feed intake and a decrease in the weight of fecal matter when compared to castor oil-treated rats (p<0.01). In castor oil-induced enter polling in rats, the EEPA produced a decrease in the weight of the intestinal content by spasmolytic activity (p<0.01). In magnesium sulfate-induced diarrhea, the EEPA treated groups showed a significant decrease in water and feed intake and a decrease in the weight of fecal matter (p<0.01). The EEPA appeared to inhibit diarrhea by reducing the absorption of water from the intestine. This is due to the presence of tannins in it. Plants and plant derivatives have important advantages such as they are cheap with less or no side effects. The findings in the present study confirm the antidiarrheal activity of the ethanolic leaf extract of Phyllanthus amarus S. thus providing the scientific basis for the traditional use of this plant in the treatment of diarrhea and its effects.

Speaker: Ms Sri Bharathi G S (Nandha College of Pharmacy, Erode )

Evaluation of antidiarrhoeal activity of ethanolic leaf extract of Phyllanthus amarus S. In wistar albino rats

26 Impact of temperature and exposure on Opuntia ficus-indica and Opuntia dillenii cladode extraction on percent yield using design expert software

The main aim of the present study is to investigate the effects of temperature and exposure time on the extraction of Opuntia ficus-indica and Opuntia dillenii cladodes. Cladodes and other parts of plants were rarely extracted for their constituents from literature. Screening, however, was not conducted to determine the influence of dependent variables on independent responses. The impact of the dependent variable on the response was determined using QbD software, namely Design Expert. A plot of Opuntia ficus-indica and Opuntia dillenii are poised, authenticated, and drenched with water to determine the effect of dependent variables (temperature and exposure time) on the response (% yield). The equation coded from this study for the percent yield was generated as +54.30+0.4061A-0.6432B+0.1500AB+0.8375A2+0.3875B2. For extraction of the contents of cladodes, 65 $^{\circ}$C is the optimal temperature and exposure time is directly proportional.

Speaker: Mr Mohammad Nizamuddin Yadiki (Jawaharlal Nehru Technological University, Anantapur)

Impact of temperature and exposure on Opuntia ficus-indica and Opuntia dillenii cladode extraction on percent yield using design expert software

27 Anti-obesity activity of Annona squamosa (Linn.) leaves extract on monosodium glutamate - High fat diet-induced obese mice model

The Methanolic extract of leaves of Annona squamosa (Linn.) has been tested for their anti-obesity property. The extracts were examined for the presence of phytoconstituents, antioxidant activity, digestive enzyme activity, hypoglycaemic effect, hypophagic effect & histology of adipose tissue, and fatty liver changes by using MSG-HFD induced obesity in Swiss albino mice. Animals treated with ASPE have reduced the increase in body weight, periepididymal fat weight, etc. The anti-obesity activity produced by ASPE may be because of inhibition of amylase enzyme, antioxidant activity, the presence of tannins, and flavonoid content. These findings suggest that the anti-obesity actions of ASPE may be partly mediated by delaying the intestinal absorption of dietary fat. The plants have shown the presence of essential phytoconstituents like sitosterols and stigmasterols in NMR, TLC, and HPTLC study whereas some common constituents like saponin, flavonoids, steroids, triterpenoids, glycosides, and anthocyanin were also present in the preliminary phytochemical study. In this study, ASPE is found to be beneficial for the suppression of obesity and some associated complications.

Speaker: Ravi Pratap Singh (Birla Institute of Technology, Mesra)

Anti-obesity activity of Annona squamosa (Linn.) leaves extract on monosodium glutamate - High fat diet induced obese mice model

Anti-obesity activity of Annona squamosa (Linn.) leaves extract on monosodium glutamate - High fat diet-induced obese mice model

28 Simultaneous detection of biogenic amines metabolites (homovanillic acid and vanillyl mandelic acid) in urine sample of rodents by HPLC-UV method

A simple, effective, and sensitive HPLC with UV detector was developed for detection of these biogenic amines metabolites in the urine sample of rodents as biotargets for neurological diseases like Parkinson’s disease, Alzheimer’s disease, Depression. The method includes the mobile phase combination of acetonitrile (ACN) and o-phosphoric acid (pH 2) in a ratio of (30:70 v/v), pH 2.2; the spectroscopic conditions were maintained for separation of analytes Kromosil C8 column 5 µm (125 X 4.6 mm) column at an ambient temperature of 25° C, at a flow rate 0.5 mL/min using EZ Chrome elite, Agilent HPLC system. Different mobile phases were used on a trial and error basis for the separation of these two metabolites. Validation of the developed method was carried out according to ICH guidelines. The calibration curve was linear over the concentration range of 10–35 μg/mL with regression coefficient (r2) 0.998 for HVA and 0.996 for VMA for both metabolite components. The limit of quantitation (LOQ) was 1 ng/mL, and the limit of detection (LOD) was 1 ng/mL. Results were satisfactory in terms of precision and accuracy. Hence, the method is suitable for the determination of homovanillic acid and vanillyl mandelic acid in urine samples.

Speaker: Vrushali Bhalchim (Dr D Y Patil Institute of Pharmaceutical Sciences & Research, Pune )

POSTER PPT VRUSHALI.pdf

Simultaneous detection of biogenic amines metabolites (Homovanillic acid and Vanillyl mandelic acid) in urine sample of rodents by HPLC-UV method.

29 A validated stability-indicating UPLC method development and forced degradation study for simultaneous quantification of ibuprofen and caffeine in capsule dosage form

A rapid and stability-indicating Ultra-Performance Liquid Chromatography (UPLC) method was developed for simultaneous quantification of Ibuprofen and Caffeine in their combined dosage form, especially to get some more advantages over other methods already developed for this combination using Photo Diode Array (PDA) detector. The separation was achieved on a UHP ASB C18 column (2.1 mm X 50 mm, 1.9 µm) at a wavelength of 254 nm, using a mobile phase A: Mobile B (Methanol: Buffer) (70:30 v/v) in an isocratic elution mode at a flow rate of 0.1 mL/min. The retention time for Ibuprofen and Caffeine was found to be 6.5 min and 1.9 min, respectively. The percentage RSD of the Ibuprofen and Caffeine were and found to be 0.6 and 0.5, respectively, and the percentage recovery was obtained at 100.3% and 100.6%. The method showed excellent linear response with correlation coefficient (R$^{2}$) values of 0.999 for both drugs. Intra-and inter-day precision studies of the new method were less than the maximum allowable limit percentage of relative standard deviation (% RSD) ≤ 2.0. The drug was subjected to acidic, alkaline media, boiling, heat, humidity, and oxidizing agent to apply stress conditions. The developed method did not show any interference of degrading peaks generated under forced degradation studies. The developed method was found to be simple, accurate, precise, and cost-effective. The forced degradation studies indicated that the degradants and excipients are within the limit. Hence, the developed method was suitable for quantitative analysis of Ibuprofen and Caffeine both in bulk and combined pharmaceutical dosage form. The study suggests that the developed UPLC method can be used for the assessment of drug purity and stability.

Bibliography:

1. Cunha RR, Chaves SC, Ribeiro MM, Torres LM, Muñoz RA, Santos WT, Richter EM. (2015) Simultaneous determination of caffeine, paracetamol, and ibuprofen in pharmaceutical formulations by high‐performance liquid chromatography with UV detection and by capillary electrophoresis with conductivity detection. J Sep Sci 38(10):1657-1662. DOI: https://doi.org/10.1002/jssc.201401387

2. Reddy YR, Kumar KK, Mukkanti K, Reddy MR. (2012) RP-UPLC method development and validation for the simultaneous estimation of ibuprofen and famotidine in pharmaceutical dosage form. Pharm Methods 3(2):57-61. DOI: https://doi.org/10.4103/2229-4708.103873

3. Kumar RV, Rao VU, KUMAR N, Subbaiah BV. (2015) A novel, rapid, and validated stability-indicating UPLC method for the estimation of Drotaverine hydrochloride and Ibuprofen impurities in oral solid dosage form. Sci Pharm 83(4):567-581. DOI: https://doi.org/10.3797/scipharm.1503-02

Speaker: Dr Carolinnimila Innacy (J K K Nattraja College of Pharmacy, Komarapalayam)

A validated stability-indicating UPLC method Development and Forced Degradation study for Simultaneous Quantification of Ibuprofen and Caffeine in Capsule Dosage Form

30 A novel instrumental method for simultaneous estimation of cardiovascular drugs

The market is flooded with a combination of drugs in various dosage forms. Multi-component formulations are in demand due to greater patient acceptability, increased potency, multiple actions, fewer side effects, and quicker relief. Analytical methods are needed to analyze multi-component formulations. Among the instrumental method for analysis, there is a renewed interest in UV Spectrophotometric methods due to methods being rapid, simple, and cost-effective compared to sophisticated HPLC, LC-MS/MS methods. Cardiovascular disease continues to occur in epidemic proportions globally. Hence multiple strategies are needed for control and reversal so as to reduce mortality and morbidity. A review of available literature indicated that ample analytical methods are available for the estimation of Metoprolol and Atorvastatin. These include HPTLC, Reverse phase HPLC methods for the drugs either individually or combined with other drugs. However, there is no reported UV-spectroscopic method for simultaneous estimation of the drugs based on the absorption correction principle. Hence, there is a need for a simple UV-spectroscopic method for the simultaneous analysis of cardiovascular drugs. A novel UV-spectroscopic method has been developed for the simultaneous estimation of cardiovascular drugs by the absorbance correction method. Methanol was used as a solvent, and water was used as a diluent for the analysis. The choice of wavelengths was based on the absorption correction principle. Accordingly, one wavelength was chosen where both drugs absorb, while the second wavelength was chosen such that only one drug was absorbed. The developed method was validated as per ICH guidelines. Linearity was obtained in the range of 10–100 µg/mL and 2–100 µg/mL for metoprolol tartrate and Atorvastatin calcium, respectively. The method was found to be accurate, precise, sensitive, and robust. The percentage assay value was found to be 99.10% for Metoprolol tartrate and 98.18% for Atorvastatin calcium which was within the acceptance criteria (90–110%). Hence, the developed UV method is a valuable, cost-effective tool for the quality control of drugs in analysis.

Speaker: Celina Nazareth (PES's Rajaram and Tarabai Bandekar College of Pharmacy, Goa)

A Novel Instrumental method for simultaneous estimation of Cardiovascular Drugs

31 Design, synthesis, biological evaluation and in-silico study of imidazopyridine linked thiazolidinone as promise anticancer agents

Design, synthesis, biological evaluation, and in-silico study of imidazopyridine-linked thiazolidinedione promise anticancer agents. A series of imidazopyridine-linked thiazolidinedione rings (6a-h) were synthesized and tested for their antiproliferative activity against a panel of three human cancer cell lines viz., MCF7 (human breast cancer), A549 (human lung cancer), and DU145 (human prostate cancer). Two compounds 6f and 6h, exhibited remarkable results against all the three cell lines, but the compound 6h was found to be the most active against breast cancer cell lines. Amongst all the synthesized compounds, 6h displayed the highest antioxidant results. Further, potent compounds 6f, and 6h showed no signs of toxicity at a dose ranging from 50 to 500 mg/kg of body weight of animals. Biochemical parameters (SGOT and SGPT) of compound 6h have nearly matched the control in hepatotoxicity studies. Molecular docking & MM-GBSA dG bind studies agree with the outcome of in vitro anticancer and antioxidant activities. The most potent compound 6h, was found to have the highest docking score, binding energy, and ADME parameters, which are in the acceptable range. Thus, it could be concluded that 6h, an imidazopyridine derivative endowed with the thiazolidinedione ring system, has the potential to be developed as an anticancer agent.

Speaker: Iqbal Md Azhar (R V Northland Institute, Dadri)

Design, synthesis, biological evaluation and in-silico study of imidazopyridine linked thiazolidinone as promise anticancer agents

32 Design, synthesis and evaluation of 5-substituted-2-amino-1,3,4-thiadiazole derivatives as anticancer agents

The present work is aimed at designing, synthesizing, and evaluating a library of 2-amino-1,3,4-thiadiazole based compounds as anticancer agents through their inhibitory action against Cyclin-Dependent Kinase (CDK2) enzyme. CDK2 is a member of the protein kinase family, which plays a major role in regulating various events of the eukaryotic cell division cycle. It is overexpressed in cancer cells, resulting in abnormal regulation of the cell cycle and hyperproliferation. Thus, CDK2 is regarded as a potential therapeutic target for cancer therapy. The 2-amino-1,3,4-thiadiazole nucleus is a privileged scaffold in drug discovery due to its diverse biological activity. One of its derivatives, 2-(4-fluorophenylamino)-5-(2,4 dihydroxyphenyl)-1,3,4-thiadiazole (FABT, 1), was shown to inhibit the extracellular signal-regulated kinase pathway to induce cell cycle arrest in human non-small lung carcinoma cells (NSCLC). A series of compounds containing the 1,3,4 thiadiazole scaffold was designed through molecular hybridization of FABT (1) with the experimental tyrosine kinase inhibitor Semaxanib (2). The designed compounds were synthesized by conventional methodologies and characterized by NMR and IR characterization techniques, followed by evaluation for their antitumor activity against C6 neuroblastoma cell line by MTT assay with doxorubicin as the reference standard. Molecular docking of each synthesized compound was done in the active site of CDK2 (PDB ID: 4LYN) using AutoDock4.2, and the binding energy was calculated. A library of compounds having general structure 3 (as shown in Figure 1) has been designed, synthesized, and evaluated for CDK2 inhibitory potential. The most potent compound of the series (compound 4) is shown to inhibit CDK2 with an IC$_{50}$ of 0.005 µM. It shows binding energy of -9.62 kcal/mol when docked with CDK2 active site (PDB ID: 4LYN) and interactions with PHE82, LEU183, ILE10, ALA31, LEU134, VAL164, ALA144, and GLU81 residues and pi-pi interaction with PHE82 and LEU83.On the basis of the above findings, it can be postulated that this rigid scaffold 3 could serve as a template for the design of potential drug candidates in cancer therapy by modulating CDK2 activity.

Bibliography:

1. Echalier A, Endicott JA, Noble ME. (2010). Recent developments in cyclin-dependent kinase biochemical and structural studies. Biochim Biophys Acta 1804(3):511-519. DOI: https://doi.org/10.1016/j.bbapap.2009.10.002.

2. Peyressatre M, Prével C, Pellerano M, Morris MC. (2015) Targeting cyclin-dependent kinases in human cancers: from small molecules to peptide inhibitors. Cancers 7(1):179-237. DOI: https://doi.org/10.3390/cancers7010179.

3. Juszczak M, Matysiak J, Szeliga M, Pożarowski P, Niewiadomy A, Albrecht J, Rzeski W. (2012) 2-amino-1, 3, 4-thiadiazole derivative (FABT) inhibits the extracellular signal-regulated kinase pathway and induces cell cycle arrest in human non-small lung carcinoma cells. Bioorg Med Chem Lett 22(17):5466-5469. DOI: https://doi.org/10.1016/j.bmcl.2012.07.036.

Speaker: Mr Rangan Mitra (Department of Pharmaceutical Indian Institute of Technology (BHU), Varanasi)

Synthesis, Characterization, Molecular Docking and Biological Evaluation of 5-Substituted-2-amino-1,3,4-thiadiazole Derivatives as Anticancer Agents

33 GC-MS fingerprinting and in-vitro biological evaluation of hydroalcoholic extract of Rosemary officinalis Linn. leaves

Rosmarinus officinalis Linn. is an aromatic perennial herb with fragrant evergreen needle-like leaves. It is member species of the Lamiaceae family. It is used commercially for antispasmodic, antimicrobial, anti-inflammatory, analgesic, antipyretic, cardiac tonic, antioxidant, antiapoptotic, anti-tumorigenic, antinociceptive, antiasthmatic, and neuroprotective properties. Our study focuses on GC-MS phytochemical analysis and biological evaluation of hydroalcoholic extract of Rosemary officinalis along with its bioassay-guided fractions viz. n-hexane and chloroform through in-vitro anti-inflammatory and antimicrobial activity. Using the solvent, hydroalcoholic extracted the Rosemary leaves via triple kinetic maceration process. Then, the obtained mother tincture of the hydroalcoholic extract was subjected to bioassay-guided fractionation using various polar and non-polar solvents such as chloroform and n-hexane. Hydroalcoholic extract's phytochemical nature and its two fractions from Rosemary officinalis were confirmed by its spectral and chromatography analysis through UV-Vis and GC-MS. Hydroalcoholic extract and its two fractions of Rosemary leaves were evaluated for their in-vitro anti-inflammatory and antibacterial activities by using various doses of 150, 250, 350 mg/kg against gram-positive (Staphylococcus aureus, Bacillus subtilis and Pseudomonas aureus) and gram-negative (Klebsiella pneumonia, Escherichia coli, and Proteus vulgaris) bacteria by agar plate diffusion method. Our study results revealed that the phytochemical screening through UV-Vis and GC-MSanalysis of hydroalcoholic extract of Rosemary leaves showed the presence of flavonoids, alkaloids, tannins, sterols, terpenes, and saponins. Further, the hydroalcoholic (HA), chloroform (CH), and n-hexane (NH) extract on in-vitro anti-inflammatory activity showed noteworthy inhibition viz. HA: 28.77%, 51.69%, and 75.49%, CH: 32.54%, 55.32%, and 78.42%, NH: 25.68%, 49.51%, and 66.82% at various doses, respectively, which was compared with standard drug Indomethacin (10 mg/kg). In addition, in-vitro antimicrobial studies showed significant inhibition on both gram-positive and gram-negative bacteria at (CH:1000 µg/mL, HA: 500 µg/mL, NH: 250 µg/mL). Our present study revealed that the chloroform fraction of Rosemary officinalis Linn possesses good antimicrobial and anti-inflammatory activities compared with the hydroalcoholic and n-hexane extracts. This promising result may be due to the rich flavonoid content in chloroform extract. However, further study is required to know the complete mechanism of these extracts on the inflammatory process and use these extracts for life-threatening problems like cancer and tuberculosis is under process.

Speaker: Ms Nithya S (Nandha College of Pharmacy, Erode)

34 Preparation and optimization of tinidazole loaded transferosomal gel

The aim of the present study is to formulate and optimize a tinidazole-loaded transfersomal gel. Transfersomes are formed by self-assembly of non-ionic surfactant and soya lecithin upon hydration with an aqueous medium resulting in a lamellar structure that encapsulates both polar and non-polar drugs. It is also a vesicular carrier for drug delivery systems. In the present research work, we prepared tinidazole transfersome using a non-ionic surfactant, span 60, and soya lecithin in a ratio of 80:20 concentration by the thin-film hydration method. These prepared tinidazole transfersomes were then incorporated into a gel which was prepared by varying concentrations of poloxamer 407. Evaluation of prepared transfersomal gels done by homogeneity, grittiness, spreadability, extrudability, drug content, in-vitro diffusion, and stability study. In this experiment performed transferosomal suspension was dispersed in carbomer and Poloxamer gel, a tinidazole transferosomal gel was created for Bacterial Vaginosis. After evaluation of both the gels, Tinidazole transfersomal gel having poloxamer as the gelling agent was found to have greater in-vitro drug release 90.41% along with the highest R2 value among all the formulations and good stability for shelf life. Tinidazole Transfersomal gel formulation provided sustained and prolonged delivery of Tinidazole in controlled manner with constant release as it follows zero-order release kinetics. The optimized formulation of transfersomal gel containing tinidazole is quite simple and stable.

Speaker: Snehal Kurhe (Shri D D Vispute College of Pharmacy and Research Center, Panvel)

Preparation and optimization of tinidazole loaded transferosomal gel

35 Pullulan based electrospun nanofibers of Voriconazole: Promising preliminary studies for oral candidiasis

Fungal infections have shown great concern with the emergence of a high threat to medically compromised patients with low immune systems, especially Candida albicans, with an increased incidence of resistance. For this reason, there is a need for developing innovative dosage forms. Hence, the main objective of this present investigation was to develop nanofibers of voriconazole using various polymers like pullulan and polyvinyl alcohol. The nanofibers fabricated by the electrospinning technique were characterized and optimized to confirm the ratios of the polymeric concentration, which ultimately affected the mechanical strength and diameter of the nanofibers. The optimized nanofibers were uniform, beadles, and 235±69 nm with an entrapment efficiency of 66.66±3.01%. The tensile strength of nanofibers was in the range of 14 g/cm$^{2}$ to 18 g/cm$^{2}$. Voriconazole-loaded nanofibers indicated a modified drug release and followed a zero-order release. The anti-fungal activity of drug-loaded nanofibers exhibits superior anti-fungal activity against Candida albicans than plain drugs. Based on these results, they indicate that nanofibers can treat oral candidiasis and can be applied as an innovative dosage form. This innovative nanofiber system can improve patient compliance and give an effective and safe therapy.

Bibliography:

1. Tuğcu-Demiröz F, Saar S, Tort S, Acartürk F. (2020) Electrospun metronidazole-loaded nanofibers for vaginal drug delivery. Drug Dev Ind Pharm 46(6): 1015-25. DOI: https://doi.org/10.1080/03639045.2020.1767125.

2. Tonglairoum P, Ngawhirunpat T, Rojanarata T, Kaomongkolgit R, Opanasopit P. (2015) Fabrication of a novel scaffold of clotrimazole-microemulsion-containing nanofibers using an electrospinning process for oral candidiasis applications. Colloids Surf B. 126:18-25. DOI: https://doi.org/10.1016/j.colsurfb.2014.12.009.

Speaker: Dr Saritha Shetty (Shobhaben Pratapbhai Patel School Of Pharmacy & Technology Management, Mumbai )

Pullulan Based Electrospun Nanofibers of Voriconazole: Promising Preliminary Studies for Oral Candidiasis

36 Formulation and evaluation of Dexketoprofen proniosomal gel

Current research is based on the development and differentiation of transdermal proniosome-based gel. The modified proniosomal gel shows good stability, release, following zero-order kinetics, maximum zeta power is ±49 mV. The pH of the whole composition was close to the skin pH 7.11 to 7.20 the drug content in the formulation was within an estimated range of 92-97%. The composition of the gel can be sorted as follows with regard to the viscosity of the drug: Dt3 > Dt2 > Dt9 > Dt7 > Dt4 > Market gel > Dt6 > Dt5 > Dt1 > Dt8. Span 40 & span 60 (50:50) proniosomal gel showed a drug release up to 12 h. The encapsulation efficiency of proniosomal gel formation ranges from 82.10% to 94.12%. Analysis of the proniosome-based niosome particle size shows that the SD (nm) particle size is 209.5 nm with a polydispersity index of 0.182.

Speaker: Ms Tanu Bhargava (Vikarm University, Ujjain)

Formulation and evaluation of dexketoprofen proniosomal gel

poster by tanu bhargava.pdf

37 Exploring the potential of curcumin and epigallocatechin in osteoarthritis by network pharmacological approach.

Osteoarthritis (OA) is a non-communicable disorder of multiple etiologies/origins, estimated to affect more than 500 million people worldwide which is 7% of the world population. while there are no pharmacological interventions other than pain management, understanding the mechanism and intertwined pathways is essential for developing a formulation addressing this multifactorial disorder. We employed a combination of software and database explorations to determine the antioxidant and anti-inflammatory properties of curcumin and green tea in this study. For data mining and network construction, PubChem, Binding database Disgenet, and Cytoscape v3.8.0 were used. Furthermore, the data was enriched using String v11.5, KEGG, and Gene Ontology (GO) to comprehend OA cellular processes and phytoconstituent’s drug potential. The possible targets associated with bioactive components of curcumin and green tea were segregated and corresponding genes associated with humans were analyzed. The protein-protein interaction (PPI) associated with genes were analyzed and possible connections of OA-associated genes with critical signaling pathways, like the Hypoxia inducible factor-1 (HIF-1) signaling pathway, Apelin signaling pathway, arginine proline metabolism, and arachidonic pathway were discovered through network pharmacological studies. The network pharmacological study found the curcumin and green tea bioactive components such as Demethoxycurcumin and Epigallocatechin gallate targets the HIF-1 signaling pathway, Apelin signaling pathway, arginine proline pathway simultaneously. Imbalance in the HIF-1 Signaling pathway leads to OA development via destabilizing the balance of Reactive Oxygen Species (ROS) in Synoviocytes. Similarly, the arachidonic pathway is associated with nitric oxide formation and oxidative stress. Curcumin and Green tea have synergistic potential action when used towards OA. In addition, the bioactive components of these molecules will be tested as potential treatments for OA and related illnesses.

Bibliography:

1. Scanzello CR, Goldring SR (2012) The role of synovitis in osteoarthritis pathogenesis. Bone 51: 249–257. DOI: https://doi.org/10.1016/j.bone.2012.02.012.

2. Hunter DJ, March L, Chew M. (2020) Osteoarthritis in 2020 and beyond: a Lancet Commission. Lancet 396: 1711–1712. DOI: https://doi.org/10.1016/S0140-6736(20)32230-3.

3. Chenevier-Gobeaux C, Simonneau C, Lemarechal H, Bonnefont-Rousselot D, Poiraudeau S, Rannou F, Ekindjian OG, Anract P, Borderie D. (2013) Effect of hypoxia/reoxygenation on the cytokine-induced production of nitric oxide and superoxide anion in cultured osteoarthritic synoviocytes. Osteoarthr Cartil 21(6): 874-881. DOI: https://doi.org/10.1016/j.joca.2013.03.010.

4. Eom DW, Lee JH, Kim YJ, Hwang GS, Kim SN, Kwak JH, Cheon GJ, Kim KH, Jang HJ, Ham J, Kang KS. (2015) Synergistic effect of curcumin on epigallocatechin gallate-induced anticancer action in PC3 prostate cancer cells. BMB Rep 48: 461–466. DOI: https://doi.org/0.5483/BMBRep.2015.48.8.216

Speaker: Srikant Garje (Poona College of Pharmacy, Pune)

Exploring the potential of curcumin and epigallocatechin in osteoarthritis by network pharmacological approach.

38 Wound healing activity of apple cider vinegar in association with a polyphenolic compound

There is a growing concern with chronic wounds in the modern medical era because they do not heal through the usual phases in an orderly and timely manner. Bacterial colonization of Staphylococcus aureus is one of the major causes of chronic wounds. Generally, the wound healing process can be potentiated by increased angiogenesis. Oxidative stress also influences wound healing as it mediates degranulation and further can exaggerate the inflammation process. ACV exhibits antioxidant, anti-inflammatory, and antimicrobial activity. It has not been widely explored for its therapeutic action as a wound-healing agent. Excessive use of apple cider vinegar can cause some side effects. To reduce the overall dosage of apple cider vinegar, an attempt is being made to study the impact of apple cider vinegar associated with a polyphenolic compound. Experimentally an initial in-vitro study was performed to determine the susceptibility of S. aureus and P. aeruginosa against different dilutions of antibiotic Streptomycin, ACV, p-coumaric acid, ACV + P-coumaric acid were assessed. Also, an in-vitro study for the antioxidant activity of ACV, p-coumaric acid, and ACV + p-coumaric acid was evaluated and the results obtained were satisfactory. Subsequent studies are essential to conclusively show the effect of ACV in association with p- coumaric acid in wound healing which is to be carried out in the ex-ovo system to assess antimicrobial, angiogenic, and antioxidant activity and will be further evaluated along with confirmatory studies in murine models.

Speaker: Ms Jegadheeswari V (Birla Institute of Technology, Mesra)

Wound healing activity of Apple Cider Vinegar in association with a Polyphenolic compound

39 A Molecular docking study for antiasthmatic targets of Manilkara zapota (L.) P. Royen leaves in treating asthma

Asthma is a chronic reversible allergic inflammatory disease of lung airways that affects millions of people worldwide; even then, only symptomatic treatment is given to control asthma. At present, the low dose inhaled corticosteroids are the standard gold treatment for asthma but have many severe side effects. So, this study aimed to search for a natural potent anti-inflammatory therapeutic agent that reverses this inflammatory disease with fewer side effects. In this, Manilkara zapota (L.) P. Royen is a medicinal plant, majorly rich in polyphenols. All the more, leaves of Manilkara zapota (L.) In traditional medical practice, Manilkara zapota (L.) P. Royen has been used to treat diseases like fever, hemorrhage, cough, and cold. In addition, previous pharmacological studies have found antioxidant, anti-inflammatory, antitumor, and antiarthritis bioactive properties. Still, no scientific data is available regarding the antiasthmatic profile of the leaves of Manilkara zapota (L.) P. Royen. In this study, phytoconstituents rich in polyphenols present in Manilkara zapota (L.) P. Royen leaves were docked with different asthmatic targets like ß-2 adrenergic receptor (PDB ID: 2RH1), leukotriene receptor (PDB ID: 6RZ6), NFк-B receptor (PDB ID: 1A3Q) via software AutoDock Vina 1.1.2. Molecular docking results revealed that Apigenin-7-rhamnoside exhibited a high affinity of -8.2 kcal/mol for the ß-2 adrenergic receptor (PDB ID: 2RH1) selected target among the studied compounds compared to standard control Formoterol with binding energy -6.4 kcal/mol. Thus, Apigenin7-rhamnoside, a flavonoid, is present in Manilkara zapota (L.) P. Royen leaves could be predicted possible as a bronchodilator agent for treating asthma. Therefore, in this experiment, an attempt was made to identify a natural potent antiasthmatic agent with the help of molecular docking, if validated in the wet lab, which could be used to treat asthma with less severe adverse effects.

Speaker: Mansi Agrawal (Birla Institute of Technology, Mesra)

A Molecular docking study for antiasthmatic targets of Manilkara zapota (L.) P. Royen leaves in treating asthma

40 Assessment of androgen receptor binding affinity of endocrine disruptors: A 2D-QSAR approach

Endocrine disruptor compounds (EDCs) are synthetic or natural molecules in the environment that promote adverse modifications of endogenous hormone regulation in humans and/or in animals. By interfering with the body’s endocrine system, these chemicals produce adverse developmental, reproductive, neurological, and immune effects in animals, abnormal growth patterns, and neurodevelopmental delays in children. Among these, certain compounds mimic the role of androgen which is responsible for controlling the development and maintenance of male sexual characteristics. In the present research, we have utilized the application of a two-dimensional quantitative structure-activity relationship (2D-QSAR) modeling technique to analyze the structural features of these chemicals responsible for binding to the androgen receptors (logRBA) in rats. We have collected the androgen receptor binding data from the EDKB database (https://www.fda.gov/scienceresearch/endocrine-disruptor-knowledge-base/accessing-edkb-database). We have then employed the DTC-QSAR tool, available at https://dtclab.webs.com/software-tools for dataset division, feature selection, and model development. This tool is a complete package providing a user-friendly, easy-to-use GUI to develop regression or classification-based QSAR models involving variable selection techniques such as genetic algorithm and best subset selection. Dataset division was done by the euclidean distance approach method followed by feature selection using the genetic algorithm (GA) technique. The best descriptor combination selection for the pooled descriptors from the best GA-derived models was done using the tool Best Subset Selection v2.1 available at https://dtclab.webs.com/softwaretools. The final partial least squares (PLS) model was evaluated using various stringent validation criteria. The developed model is robust, predictive, and should be a useful tool to predict the binding nature of EDCs to the androgen receptor. From the model, we interpreted that hydrophobicity in terms of octanol-water partition coefficient, aliphatic -CH group count, the bulkiness of the structure, in addition to a number of non-aromatic conjugated carbon atoms (sp2 hybridized), presence of CF$_{3}$ group, percentage of nitrogen present in the compounds contribute to the receptor binding affinity and thus increase toxicity, while the presence of electron-rich features like aromaticity in a molecule and presence of polar groups like alcohol, phenol or carboxyl groups decrease the receptor binding affinity and reduce toxicity. Additionally, we have also performed chemical read-across using Read-Across-v2.0 available from https://sites.google.com/jadavpuruniversity.in/dtc-lab-software/home, and the results for the external validation metrics were found to be better in the euclidean distance-based similarity considerations.

Bibliography:

1. Fang H, Tong W, Branham WS, Moland CL, Dial SL, Hong H, Xie Q, Perkins R, Owens W, Sheehan DM. (2003) Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor. Chem Res Toxicol 16(10): 1338-1358. DOI: 10.1021/tx030011g

2. Waller CL, Juma BW, Gray Jr LE, Kelce WR. (1996). Three-dimensional quantitative structure–activity relationships for androgen receptor ligands. Toxicol Appl Pharmacol 137(2): 219-227. DOI: https://doi.org/10.1006/taap.1996.0075

Speaker: Arkaprava Banerjee (Jadavpur University, Kolkata)

Assessment of Androgen Receptor Binding Affinity of Endocrine Disruptors: A 2D-QSAR Approach

16:45 Tea Break

Valedictory Ceremony

5.00-5.15 PM: Welcome address by Dr. Trishna Bal
5.15-5.30 PM: Program summary by Prof. Venkatesan Jayaprakash
5.30-5.45 PM: Prize announcement & Feedback by Prof. Swastika Ganguly
5.45-6.00 PM: Vote of Thanks by Dr. Animesh Ghosh

Convener: Anima Pandey (Birla Institute of Technology, Mesra)