Taccalonolide microtubule stabilizers

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

This review focuses on a relatively new class of microtubule stabilizers, the taccalonolides. The taccalonolides are highly oxygenated pentacyclic steroids isolated from plants of the genus Tacca. Originally identified in a cell-based phenotypic screen, the taccalonolides have many properties similar to other microtubule stabilizers. They increase the density of interphase microtubules, causing microtubule bundling, and form abnormal multi-polar mitotic spindles leading to mitotic arrest and, ultimately, apoptosis. However, the taccalonolides differ from other microtubule stabilizers in that they retain efficacy in taxane resistant cell lines and in vivo models. Binding studies with the newly identified, potent taccalonolide AJ demonstrated covalent binding to β-tubulin at or near the luminal and/or pore taxane binding site(s) which stabilizes microtubule protofilaments in a unique manner as compared to other microtubule stabilizers. The isolation and semi-synthesis of 21 taccalonolides helped to identify key structure activity relationships and the importance of multiple regions across the taccalonolide skeleton for optimal biological potency.

Original languageEnglish (US)
Pages (from-to)5091-5096
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume22
Issue number18
DOIs
StatePublished - Sep 15 2015

Fingerprint

Microtubules
Tubulin
Steroids
Binding Sites
Cells
Apoptosis
Dioscoreaceae
Phytosterols
Spindle Apparatus
Interphase
Structure-Activity Relationship
taxane
Skeleton
Cell Line
taccalonolide AJ

Keywords

  • Laulimalide
  • Microtubule
  • Microtubule stabilizer
  • Paclitaxel
  • Tacca
  • Taccalonolide
  • Taxol
  • Tubulin

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Taccalonolide microtubule stabilizers. / Li, Jing; Risinger, April L; Mooberry, Susan L.

In: Bioorganic and Medicinal Chemistry, Vol. 22, No. 18, 15.09.2015, p. 5091-5096.

Research output: Contribution to journalArticle

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