title: Identification and biological activities of new taccalonolide microtubule stabilizers.
abstract: The taccalonolides are a unique class of microtubule stabilizers that do not bind directly to tubulin. Three new taccalonolides, Z, AA, and AB, along with two known compounds, taccalonolides R and T, were isolated from Tacca chantrieri and Tacca integrifolia. Taccalonolide structures were determined by 1D and 2D NMR methods. The biological activities of the new taccalonolides, as well as taccalonolides A, B, E, N, R, and T, were evaluated. All nine taccalonolides display microtubule stabilizing activity, but profound differences in antiproliferative potencies were noted, with IC(50) values ranging from the low nanomolar range for taccalonolide AA (32 nM) to the low micromolar range for taccalonolide R (13 μM). These studies demonstrate that diverse taccalonolides possess microtubule stabilizing properties and that significant structure-activity relationships exist. In vivo antitumor evaluations of taccalonolides A, E, and N show that each of these molecules has in vivo antitumor activity.
authors.affiliation: Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA. Pengj2@uthscsa.edu
authors.forename: Jiangnan
authors.initials: J
authors.lastname: Peng
authors.forename: April L
authors.initials: AL
authors.lastname: Risinger
authors.forename: Gary A
authors.initials: GA
authors.lastname: Fest
authors.forename: Evelyn M
authors.initials: EM
authors.lastname: Jackson
authors.forename: Gregory
authors.initials: G
authors.lastname: Helms
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Polin
authors.forename: Susan L
authors.initials: SL
authors.lastname: Mooberry
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D027743:Dioscoreaceae / Q000737:chemistry; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects; D027343:Rhizome / Q000737:chemistry; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D013256:Steroids; C475870:taccalonolide A