Synthesis of novel indolizine, diazepinoindolizine and Pyrimidoindolizine derivatives as potent and selective anticancer agents

Abstract

A series of new indolizine 9a–c, 10a–c, diazepinoindolizine 7a–c, 8a–c, and pyrimidoindolizine 11 derivatives were synthesized and structures of the newly synthesized compounds were confirmed by spectral and elemental analyses. Antitumor activity evaluation was carried out using sulphorhodamine-B assay method against lung adenocarcinoma (A549), breast (MCF7), hepatoma (Hep3B) cancer cell lines and normal fibroblast cells. Compounds 7a, 9c, 10a,c and 11 showed to be the most active against the lung cancer cell line with IC50 in nanomole range (16–85 nmol/ml) and compound 11 was the best selective one (S. I. = 19). The most potent compounds against MCF7 are 8c, 9b,c, 10a,b, and 11. Their IC50 range is 4–46 nmol/ml and the best selectivity was assigned for compound 11 (S. I. = 133). As for the hepatoma cancer cell line, compounds 7a, 8a–c, 9a–c, and 10a,b were found to be the most potent with IC50 range 3–90 nmol/ml and compound 8c was the most selective one (S. I. = 42), the rest of the new compounds showed IC50 value >100 nmol/ml. Compound 10a showed a broad spectrum activity and selectivity against the tested cell lines with a much lesser effect on normal fibroblast cells (IC50 > 200 nmol/ml).