Synthesis of pyridine, pyran and thiazole containing thiophene derivatives and their anti-tumor evaluations

The multi-component reaction of 2-acetylthiophene with aromatic aldehydes and either malononitrile or ethyl cyanoacetate gave the pyran derivatives 4a–4f and pyridine derivatives 5a–5f. On the other hand, the reaction of the 2-acetylthiophene with elemental sulfur and either malononitrile or ethyl cyanoacetate gave the thiophene derivatives 6a and 6b; respectively. Compounds 6a and 6b underwent a series of heterocyclic reactions to give thiazole and thiophene derivatives. All the products were assessed for antitumor activity towards human cancer human gastric cancer (NUGC and HR), human colon cancer (DLD1), human liver cancer (HA22T and HEPG2), human breast cancer (MCF), nasopharyngeal carcinoma (HONE1) cell lines. Compounds 4e, 4f, 5e, 5f, 7b, 8b, 10e, 10f, 11e, 11f, 14d-f, 15d-f, 16a,b and 18b exhibited optimal cytotoxic effect against cancer cell lines, with IC50’s in the nM range. Moreover, 7b, 10e, 14d, 15e and 16b showed no toxicity against shrimp larvae. Anti-proliferative cell activity against cancer cell lines of the most potent compounds showed that compounds 5f and 10e achieved the highest activities among the tested compounds.