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OBJECTIVE - The present study is to design, synthesize and molecular docking of triazolothiadiazole derivatives as potential anticancer agents.
METHOD – Eleven new derivatives of imidazopyridine linked triazolothiadiazole were synthesized in three steps, and their chemical structures of the title compounds (9a-k) were proved by IR, 1H NMR, 13C NMR, Mass spectroscopic and elemental analyses. The in-vitro anticancer screening at National Cancer Institute (NCI, USA) - a Chemotherapeutic Research Division under the Development Therapeutic Program (DTP) against a panel of NCI 60 tumor cell lines which included nine human systems as Melanoma, Leukemia, and cancers of Brain, Breast, Colon, Kidney, Lung, Ovary, and Prostate, according to their own protocol.
RESULT – The Anticancer activity of title compounds (9a-k) were tested and found the compound 9a exhibited 63.54% growth against UO-31 cell line, compound 9b exhibited 66.83% growth against A498 cell line, compound 9c exhibited 72.03% growth against UO-31 cell line, compound 9d exhibited 93.06% growth inhibition against RXF 393 cell line (Renal cancer), compound 9f exhibited 68.73% growth against UO-31 cell line, compound 9g exhibited 46.71% growth against HL-60(TB) cell line (Leukemia cancer), compound 9h exhibited 57.26% growth against UO-31 cell line and compound 9i exhibited 11.48% growth against K-562 cell line (Leukemia cancer) which is comparable to reference drug doxorubicin and showed good binding affinity against EGFR TK by molecular docking.
The compound 9d exhibited remarkable anticancer activity at multiple dose levels against all 60 tumor cell lines distributed among nine subpanels with GI50 ranging from 0.459 to 21.5 μM. By virtue of sensitivity against few individual cell lines, the compound displayed high activity against cell lines SNB-75, A498, UO-31, MOLT-4, and HOP-92 with GI50 values of 0.459, 1.11, 1.13, 1.15, and 1.19 μM respectively and moderate sensitivity towards cell lines viz. SK-OV-3, SF-268, OVCAR, and UACC-257 with GI50 values of 21.5, 3.99, 3.44, and 3.00 μM, respectively.
CONCLUSION - Among these, compound 9d was further selected for the next level of screening i.e. five dose assays at different concentrations (0.01, 0.1, 1, 10 & 100 μM) against NCI-60 tumor cell lines.