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.
Srivastava
Sanjay K
SK
Divisions of Medicinal Chemistry, Dabur Research Foundation, 22, Site IV, Sahibabad, Ghaziabad, India. srivastavasa@dabur.com
Abraham
Aji
A
Bhat
Beena
B
Jaggi
Manu
M
Singh
Anu T
AT
Sanna
Vinod K
VK
Singh
Gurvinder
G
Agarwal
Shiv K
SK
Mukherjee
Rama
R
Burman
Anand C
AC
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D051379:Mice; D008956:Models, Chemical; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones
D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C002602:costunolide; D007783:Lactones