Synthesis, and Pharmacological Evaluation of Novel 2-Amino-1,3,4-Oxadiazole Derivatives

Abstract

Oxadiazole is one of the vibrant heterocyclic nucleus and an important pharmacophore in the field of drug designing and discovery because of its diverse biological activities. The research conducted is focused on synthesis, biological activities and virtual screening of 2-(substituted phenyl)-1, 3, 4-oxadiazol-5-yl] benzamide derivatives. First 5-(substituted phenyl)-1, 3, 4- oxadiazol-2-amine was synthesized by reacting semicarbazide hydrochloride with 4- chlorobenzaldehyde and pyridine-3-carbaldehyde. These 2-amino-1, 3, 4-oxadiazole nuclei were further converted to corresponding amide derivatives by reaction with different benzoic acids in presence of dicyclohexyl carbodiimide (DCC) using acetonitrile as solvent. Newly synthesized derivatives were assessed for potential anti-inflammatory activity. Compound 1c was found to be most potent cyclooxygenase inhibitor with maximum mean paw volume displacement 0.233 (±) 0.012. Overall anti-inflammatory activity of all derivatives was found to be average as compared to standard drug. All eight newly synthesized compounds were docked against cyclooxygenase-2 (5F1A) to establish their binding potential. In-silico studies showed the interaction between newly synthesized compounds and cyclooxygenase-2 enzyme depending on both hydrophobic forces and conventional hydrogen bonds. Highest binding affinity was found to be -9.6 Kcal/mol by compound 1c which is greater than the binding affinity of standard molecule diclofenac sodium. These results suggested that 2-[substituted phenyl)-1, 3, 4-oxadiazol-5-yl] benzamide might be used as lead compound for further designing and manipulating new potential cyclooxygenase-2 inhibitors.