Synthesis, characterization and in vivo antitumor effect of new α,β-unsaturated-2,5-disubstituted-1,3,4-oxadiazoles

Abstract

New α,β-unsaturated-2,5-disubstituted-1,3,4-Oxadiazoles (4a–j) and (10a–d) have been prepared in good to excellent yields starting from β-chlorovinyl aldehydes and hydrazide. The synthesized oxadiazoles were fully characterized by (¹H, ¹³C) NMR, IR and HRM Sspectroscopic techniques. The in vivo antitumor activity of 4b, 4c, 4g, 4d, and 10c was evaluated. Biochemical measurements of serum alanine aminotransferase, aspartate aminotransferase and creatinine levels of mice injected with a dose of 20 mg/kg, of each selected compound, showed no toxic effect, neither in liver nor in kidney organs. However, hepato/nephrotoxicities were observed in mice treated with a dose of 100 mg/kg. When tested on melanoma in a mice xenograft model, the pharmacodynamic study indicated that the two compounds 4c, bearing a trifluoromethyl group and 10c, bearing a triazole moiety, are potent antitumoral agents at the safe dose of 20 mg/kg against B16-F10-induced melanoma.

Graphical Abstract

Keywords:

• β-Chlorovinyl aldehydes
• toxicity
• B16-F10 melanoma
• α,β-unsaturated-2,5-disubstituted-1,3,4-oxadiazoles

Acknowledgements

We are grateful to the Tunisian Ministry of High Education and Scientific Research (LR99ES14) and the LG2A-UMR7378-CNRS research group in France for financial support of this research.