title: Hydrolysis reactions of the taccalonolides reveal structure-activity relationships.
abstract: The taccalonolides are microtubule stabilizers isolated from plants of the genus Tacca that show potent in vivo antitumor activity and the ability to overcome multiple mechanisms of drug resistance. The most potent taccalonolide identified to date, AJ, is a semisynthetic product generated from the major plant metabolite taccalonolide A in a two-step reaction. The first step involves hydrolysis of taccalonolide A to generate taccalonolide B, and then this product is oxidized to generate an epoxide group at C-22-C-23. To generate sufficient taccalonolide AJ for in vivo antitumor efficacy studies, the hydrolysis conditions for the conversion of taccalonolide A to B were optimized. During purification of the hydrolysis products, we identified the new taccalonolide AO (1) along with taccalonolide I. When the same hydrolysis reaction was performed on a taccalonolide E-enriched fraction, four new taccalonolides, assigned as AK, AL, AM, and AN (2-5), were obtained in addition to the expected product taccalonolide N. Biological assays were performed on each of the purified taccalonolides, which allowed for increased refinement of the structure-activity relationship of this class of compounds.
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, Texas 78229, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Jiangnan
authors.initials: J
authors.lastname: Peng
authors.forename: April L
authors.initials: AL
authors.lastname: Risinger
authors.forename: Susan L
authors.initials: SL
authors.lastname: Mooberry
mesh_terms: D049109:Cell Proliferation; D027743:Dioscoreaceae / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008870:Microtubules / Q000187:drug effects*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D013256:Steroids; C570719:taccalonolide AJ; C475869:taccalonolide E