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2014 ; 22
(18
): 5091-6
Nephropedia Template TP
Bioorg Med Chem
2014[Sep]; 22
(18
): 5091-6
PMID24491636
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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 ?-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.
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