Synthesis and biological evaluation of thiazolo[3,2-b][1,2,4]triazole substituted 1,3,4-oxadiazole and pyridine derivatives as anticancer agents

A new series of thiazolo[3,2-b][1,2,4]triazole substituted 1,3,4-oxadiazole and pyridine derivatives (17a-j) were synthesized by the cyclization of thiazolo[3,2-b][1,2,4]triazole carbohydrazide and differently substituted benzoic acids. The structures of these derivatives were characterized by ¹HNMR, ¹³CNMR and mass spectral data and anticancer activities were determined by MTT assay method against human prostate cancer (PC3), human lung cancer (A549), human breast cancer (MCF-7) & human ovarian cancer (DU-145) cell lines with etoposide used as positive control. The Structure Activity Relationship studies showed that the drug candidate 17a with 3,4,5-trimethoxy electron donating substituent on phenyl ring showed potent anticancer activities against PC3, A549, MCF-7 and DU-145 cell lines with IC₅₀ values of 0.14 ± 0.065 μM, 0.10 ± 0.084 μM, 0.04 ± 0.0076 μM, and 0.19 ± 0.082 μM. The compound 17a was docked with the X-ray crystal structure of PDK1 with (PDB ID 1OKY) to elucidate the interactions between the small molecule and the active site residues and having a binding energy of −7.9 kcal/mol.