Synthesis, characterization and cytotoxic evaluation of novel derivatives of 1, 3, 4-oxadiazole containing 5-phenyl thiophene moiety

Abstract

In the present work a series of novel derivatives of 1,3,4-oxadiazoles containing 5-phenyl thiophene moiety has been synthesized by convergent synthetic method and studied their anticancer properties. The synthesized compounds were characterized by spectral ( 1 H-NMR, 13 C NMR, MS and elemental) analyses. Three cell lines were used for thecytotoxic evaluation namely, HepG2, Caco-2 and PANC-1. The synthetic chemistry involved conversion of various substituted aromatic acids into ethyl ester 2a-e. The ethyl ester was converted into corresponding carbohydrazide 3a-e. Carbohydrazides3a-e were reacted with 5-phenyl thiophene-2- carboxaldehyde(5) in presence of acetic acid as catalyst and obtained novel Schiff base compounds6a-e. The Schiff base derivatives were cyclized using chloramine-T as promoter and obtained novel derivatives of 1,3,4- oxadiazole 7a-e.Among the synthesised compounds, the cytotoxicity of the compound 7b i.e. 2-(4'- fluorobiphenyl-3-yl)-5-(5-phenylthiophen-2-yl)-1,3,4-oxadiazole against Caco-2 cell line with IC50 of 5.3µM. The compound 7e i.e.2-(4-methoxyphenyl)-5-(5-phenylthiophen-2-yl)-1,3,4-oxadiazoleshowed moderate cytotoxicity against HepG2 with IC50 of 28.4µM. Rest of the compounds showed less cytotoxicity against all the