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Taccalonolide microtubule stabilizers.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2014 Sep 15; Vol. 22 (18), pp. 5091-6. Date of Electronic Publication: 2014 Jan 15. - Publication Year :
- 2014
-
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.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Antineoplastic Agents, Phytogenic chemistry
Antineoplastic Agents, Phytogenic isolation & purification
Humans
Microtubules metabolism
Models, Molecular
Molecular Conformation
Steroids chemistry
Steroids isolation & purification
Structure-Activity Relationship
Tubulin Modulators chemistry
Tubulin Modulators isolation & purification
Antineoplastic Agents, Phytogenic pharmacology
Microtubules drug effects
Steroids pharmacology
Tubulin Modulators pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 22
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 24491636
- Full Text :
- https://doi.org/10.1016/j.bmc.2014.01.012