Abstract
The pursuit of discovering efficacious novel anticancer agents is an ongoing and perpetual endeavour. The ongoing research endeavour involves the discovery of a new set of various substituted 1,2,4-triazole carboxamide derivatives. The synthetic process involves multiple steps: converting thiooxamic acid ethyl ester to ethyl b-N-boc-oxalamidrazone (2), preparing ethyl esters of 5-substituted 1,2,4-triazole-3-carboxylic acid (3) and synthesizing 5-substituted 1,2,4-triazole-3-carboxylic acid amides (4a-n) using potassium tert.-butoxide. The resulting compounds are characterized using 1H and 13C NMR spectroscopy and HRMS. Molecula docking experiments were performed using the synthesized compounds against two cancer targets, viz. EGFR (6LUD) and CDK-4 (7SJ3). The compounds were assessed for their anticancer potential against four different cancer cell lines, namely non-small cell lung cancer (A-549), pancreatic cancer (PANC-1), colorectal cancer (HCT-116) and cervical cancer (HaLa) cell lines. Additionally, a normal human embryonic kidney cell line (HEK-293) was used for comparison. The results obtained from molecular docking analysis demonstrated that the 1,2,4-triazole carboxamides (4c, 4e, 4h, 4m and 4n) exhibited more favourable binding interactions compared to the ligands that were co-crystallized. All the compounds exhibited a satisfactory cytotoxicity profile in comparison to the reference drug doxorubicin. Among the compounds that tested, it was observed that compounds 4e and 4m displayed the most pronounced inhibitory activity across all the cell lines that were tested.
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