Synthesis and biological evaluation of some new pyrimidine bearing 2,5-disubstituted 1,3,4-oxadiazole derivatives as cytotoxic agents

Abstract

Objective: As a result of adverse effects including drug-resistance, toxicity and low bioavailability, there has been a crucial need for novel anticancer agents. In this present study, some novel 2,5-disubstituted 1,3,4-oxadiazole derivatives bearing pyridine moiety were synthesized and their potential cytotoxic activities were examined. Materials and methods: A series of seven new compounds of 2-[(5-(3-(pyrimidin-2-yl) thio) propyl)-1,3,4-oxadiazol- 2-yl) thio)]-1-(4-substituted) ethan-1-one derivatives were synthesized by reacting 5-[(3-(pyrimidin-2-yl) thio) propyl]-1,3,4-oxadiazole-2-thiol and 4-substituted phenacyl bromide derivatives in acetone with potassium carbonate. The structures of the obtained compounds were elucidated using FT-IR, 1H-NMR and MS spectral data and elemental analyses. In vitro cytotoxic activity of the compounds was evaluated by MTT assay. Results: Among the tested compounds, compound 4a was found to be the most active cytotoxic agent against A549 cells, in compared with cisplatin as standard drug. Conclusions: It was determined that some of synthesized compounds had considerable anticancer activity against the A549 cell lines. Compound 4a including phenyl moiety was the most active compound against the A549 cell line and was identified as a lead moiety. Besides, compound 4c including 4-metoxy phenyl moiety exhibited cytotoxic activity against A549 cells. Consequently, compounds possess phenyl and 4-methoxy phenyl moieties have been determined to be important for cytotoxic activity of these compounds.