Synthesis of 13-amino costunolide derivatives as anticancer agents

A number of costunolide derivatives (4a-p) have been synthesized and evaluated for their in vitro cytotoxicity against eight tumor and a non-tumor cell lines. Compound 4d showed around 2-fold better cytotoxicity against SW-620 (colon) cell line with improved safety index than costunolide (1). While compounds 4e, 4g, and 4p have shown around 2- to 3-fold better cytotoxicity against MIAPaCa2 (pancreas), K-562 (leukemia) and PA-1 (ovary) cell lines as well as better safety index in comparison to costunolide (1). Compound 4p also exhibited cytotoxicity against HBL100 (breast) cell line with 2-fold better safety index. Structure-activity relationship has been described.