title: 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.
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, Del Shankel Structural Biology Center, 2034 Becker Drive, West Campus, Lawrence, Kansas 66047.
authors.forename: Hashim F
authors.initials: HF
authors.lastname: Motiwala
authors.forename: Joseph
authors.initials: J
authors.lastname: Bazzill
authors.forename: Abbas
authors.initials: A
authors.lastname: Samadi
authors.forename: Huaping
authors.initials: H
authors.lastname: Zhang
authors.forename: Barbara N
authors.initials: BN
authors.lastname: Timmermann
authors.forename: Mark S
authors.initials: MS
authors.lastname: Cohen
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Aubé
keywords: DRO81-1; Withalongolide A; jaborosalactone; macrocycle; triacetate; withaferin A