Open AccessSynthesis and Cytotoxicity of Semisynthetic Withalongolide A Analogues
Author(s) -
Hashim F. Motiwala,
Joseph Bazzill,
Abbas Samadi,
Huaping Zhang,
Barbara N. Timmermann,
Mark S. Cohen,
Jeffrey Aubé
Publication year - 2013
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/ml400267q
Subject(s) - withaferin a , cytotoxicity , cytotoxic t cell , chemistry , cancer cell lines , natural product , stereochemistry , cell culture , structure–activity relationship , cancer cell , biochemistry , cancer , biology , in vitro , medicine , withania somnifera , genetics , alternative medicine , pathology
The natural product withaferin A exhibits potent antitumor activity and other diverse pharmacological activities. The recently discovered withalongolide A, a C-19 hydroxylated congener of withaferin A, was recently reported to possess cytotoxic activity against head and neck squamous cell carcinomas. Semisynthetic acetylated analogues of withalongolide A were shown to be considerably more cytotoxic than the parent compound. To further explore the structure-activity relationships, 20 new semisynthetic analogues of withalongolide A were synthesized and evaluated for cytotoxic activity against four different cancer cell lines. A number of derivatives were found to be more potent than the parent compound and withaferin A.