Design and Synthesis of Novel 1a,3,4-Oxadiazole Derivatives as Cytotoxic Agents: A Combined Experimental and Docking Study

Abstract

A novel series of 3,5-disubstituted-1a,3,4-oxadiazole derivatives was synthesized and screened for in vitro anticancer activity. The newly synthesized compounds were characterized by 1H, 13C NMR, IR spectroscopy and mass spectrometry. Among all the synthesized compounds, Oxaprozin derivatives containing 1,3,4-oxadiazole ring with 4-fluorobenzyl, 4-methoxybenzyl, methyl, and butyl substituents showed promising anticancer activity against HTB-57 cancer cell line, and derivatives with 4-fluorobenzyl, 4-methoxybenzyl, and propyl substituents exhibited a higher anticancer activity against a PPC-1 cell line. The possible binding mode interactions of the synthesized compounds with the key active site of the proline rich tyrosine kinase 2 Pyk2 receptor (PDB ID: 5TO8) were investigated using the AutoDock 4.2 docking protocol to find that the 1,3,4-oxadiazole Oxaprozin derivatives with methyl, ethyl, and propyl substituents had the highest binding energies (ΔG = –7.8, –7.6, and –6.8 kcal/mol, respectively) with Glu441, Leu431, Ala455, Val487, Met502, Leu556, Lys457, and Glu509.