Uses of acetoacetanilide for the synthesis of thiophene derivatives with cytotoxic activities

Abstract

The reaction of acetoacetanilide 1 with elemental sulfur and malononitrile 2 gave the thiophene derivative 3. The latter was the key starting material for the synthesis of different thiophene and fused derivatives through its reaction with aryldiazonium chloride, benzaldehyde and acetic anhydride. Moreover, the reaction with phenylisothiocyanate produced fused derivative. The reaction of compound 3 with elemental sulfur produced dithiophene derivative. In addition, the reaction of compound 3 with ethylcyanoacetate produced N-cyanoacetamide derivative that was capable for further heterocyclizations through its reaction with different reagents. The cytotoxicity of the newly synthesized products was evaluated against the three cancer cell lines namely MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer), and SF-268 (CNS cancer) where some compounds showed optimal cytotoxicity. The results showed that compounds 5a, 5b, 8, 22, and 23 exhibited optimal cytotoxic effect against cancer cell lines.

KEY WORDS: Thiophene, Thieno[2,3-d]pyrimidine, Coumarin, Cytotoxicity

Bull. Chem. Soc. Ethiop. 2017, 31(3), 519-534.   

DOI: http://dx.doi.org/10.4314/bcse.v31i3.16