Identification and biological activities of new taccalonolide microtubule stabilizers

Jiangnan Peng, April L. Risinger, Gary A. Fest, Evelyn M. Jackson, Gregory Helms, Lisa A. Polin, Susan L. Mooberry

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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 IC50 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.

Original languageEnglish (US)
Pages (from-to)6117-6124
Number of pages8
JournalJournal of Medicinal Chemistry
Volume54
Issue number17
DOIs
StatePublished - Sep 8 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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