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 f 0.065 mu M, 0.10 f 0.084 mu M, 0.04 f 0.0076 mu M, and 0.19 f 0.082 mu M. 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.