Synthesis of 13-amino costunolide derivatives as anticancer agents

  • Bioorg Med Chem Lett. 2006 Aug 15;16(16):4195-9. doi: 10.1016/j.bmcl.2006.05.083.
Sanjay K Srivastava  1 ,  Aji Abraham ,  Beena Bhat ,  Manu Jaggi ,  Anu T Singh ,  Vinod K Sanna ,  Gurvinder Singh ,  Shiv K Agarwal ,  Rama Mukherjee ,  Anand C Burman
Affiliations
  • 1. Divisions of Medicinal Chemistry, Dabur Research Foundation, 22, Site IV, Sahibabad, Ghaziabad, India. [email protected]
PMID: 16766184 DOI: 10.1016/j.bmcl.2006.05.083
Abstract

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.