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Synthesis and Cytotoxicity of Semisynthetic Withalongolide A Analogues.

ABSTRACT: 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.

SUBMITTER: Motiwala HF

PROVIDER: S-EPMC3835334 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Synthesis and Cytotoxicity of Semisynthetic Withalongolide A Analogues.

Motiwala Hashim F HF Bazzill Joseph J Samadi Abbas A Zhang Huaping H Timmermann Barbara N BN Cohen Mark S MS Aubé Jeffrey J

ACS medicinal chemistry letters 20131101 11

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 semisynt ...[more]

PMID: 24273633

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