LAUSR

Novel thiophene derivatives 3a–f were synthesized by using the 3-oxo-3-propanenitrile derivatives 1a–c with triethylamine, elemental sulfur and either of malononitrile or ethyl cyanoacetate. Compounds 3a, 3c, and 3e were reacted with ethyl cyanoacetate to give the 2-(N-cyanoacetamido)-thiophene derivatives 4a–f. The latter compounds underwent ready cyclization in sodium ethoxide to give the thieno[2,3-b]pyridine derivatives 5a–f. Compounds 5a–f underwent [4 + 2] cycloaddtion to produce the quinoline derivatives 7a–f. The newly synthesized 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) and normal fibroblast (WI38) cell lines. Excellent antitumor activities were shown by compounds 3c, 3d, 4b, 5b, 8c, 8d, 9a, 9c, 9d, 11d, and 15d, where they exhibited optimal cytotoxic effect against the cancer cell lines, with IC50s in the nM range. Compounds 11d and 3c showed the maximum inhibitory effect and these are much higher than the reference CHS-828.