Identification and Biological Activities of New Taccalonolide Microtubule Stabilizers

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• 作者：Jiangnan Peng ; April L. Risinger ; Gary A. Fest ; Evelyn M. Jackson ; Gregory Helms ; Lisa A. Polin ; Susan L. Mooberry
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：September 8, 2011
• 年：2011
• 卷：54
• 期：17
• 页码：6117-6124
• 全文大小：882K
• 年卷期：v.54,no.17(September 8, 2011)
• ISSN：1520-4804

文摘

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 IC₅₀ values ranging from the low nanomolar range for taccalonolide AA (32 nM) to the low micromolar range for taccalonolide R (13 渭M). These studies demonstrate that diverse taccalonolides possess microtubule stabilizing properties and that significant structure鈥揳ctivity relationships exist. In vivo antitumor evaluations of taccalonolides A, E, and N show that each of these molecules has in vivo antitumor activity.