Pharmaceutical Research
&
Innovations in Pharma Industry

Novel heterocyclic oxadiazoles viz. 2-subsituted-5-(4-pyridyl)-1,3,4-oxadiazoles, 2-subsituted-5-(3pyridyl)-1,3,4-oxadiazoles and 2-subsituted-5-(phenyl or 4-chlorophenyl-1,3,4-oxadiazoles) were designed and synthesized as poten al an cancer agents. In this inves ga on, all compounds were evaluated for their COX-1 and COX-2 inhibitory ac vity in vitro as new therapeu c approaches assumed cytotoxic eff ect associated with selec ve COX-2 inhibi on. Results showed that most of the deriva ves demonstrated inhibi on towards both isoforms of COX comparable to the standard reference drugs indomethacin, diclofenac sodium and celecoxib. Then, nine selected compounds were subjected to cytotoxic screening against UO-31 renal cancer cell line using MTT assay. Three vompounds displayed promising behavior by showing good an cancer ac vity. Moreover, kinase inhibitory assay against the tyrosine kinase EGFR was performed for the three compounds showing the highest cytotoxic ac vity. The tested compounds were potent against EGFR with the highest ac vity being observed for compound X showing nearly double the potency of the reference drug Erlo nib. Moreover, molecular docking and molecular dynamics were performed for against EGFR, in an a empt to elucidate a model for this class binding at the molecular level, simulate and understand the possible binding interac ons underlying the associa on between these small molecules and the kinase enzyme ATP binding pocket essen al amino acids. Finally, in silico pharmacokine c profi le predica on was inves gated for X using SWISS/ADME to iden fy the most promising small-molecule cytotoxic agent on the basis of displaying the best drug-like proper es. Results indicated that compound X has a poten al to serve as a lead compound for developing novel an cancer therapeu c agents.