New Approaches for the Synthesis of Thiophene Derivatives with Anti-tumor Activities

Abstract

The reaction of either cyclohexanone or cyclopentanone with cyanoacetylhydrazine and elemental sulfur gave the 2-aminocycloalkeno[b]thiophene derivatives 3a and 3b, respectively. The latter compounds reacted with either aromatic benzaldehydes or active methylene reagents to give the Schiff’s bases 5a–d and the pyrazole derivatives 7a–d and 9a–d, respectively. On the other hand, the reaction of 3-oxo-N-p-tolylbutanamide (10) with either of malononitrile or ethyl cyanoacetate gave the thiophene derivatives 13a and 13b, respectively. Compounds 13a,b were subjected to a series of heterocyclization reactions to give heterocyclic derivatives. Their cytotoxicity against the three human tumor cells lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) together against the normal human cell line namely the normal fibroblast cells WI 38 were measured.