The taccalonolides are a class of microtubule stabilizing agents isolated from plants of the genus Tacca. Functionally, they resemble the taxane drug paclitaxel (and docetaxel, a synthetic derivative of the naturally occurring compound paclitaxel), which disrupts microtubule function, inhibiting cell replication. One of the roles of normal microtubules is to aid in the replication of cells, and paclitaxel promotes the formation of microtubules that do not function properly, thus disrupting this function and inhibiting cell replication. Suppression of bone marrow function is the principal adverse side effect associated with paclitaxel treatment.

In the current study, investigators at the University of Texas Health Science Center (San Antonio, USA) sought an explanation at the molecular level as to how the taccalonides interact with and stabilize microtubules.

They reported in the November 1, 2011, online edition of the Journal of the American Chemical Society that they had isolated five new taccalonolides, AC–AF and H2, from one fraction of an ethanol extract of Tacca plantaginea. Taccalonolide AJ, an epoxidation product of taccalonolide B, was generated by semisynthesis. Structures of the compounds were elucidated using a combination of spectroscopic methods, including NMR (nuclear magnetic resonance) and high-resolution mass spectroscopy.

Five of these taccalonolides demonstrated cellular microtubule-stabilizing activities and antiproliferative actions against cancer cells. In mechanistic assays, taccalonolides AF and AJ stimulated the polymerization of purified tubulin, an activity that had not previously been observed for taccalonolides A and B, providing the first evidence that this class of microtubule stabilizers can interact directly with tubulin/microtubules.

“We have been working with these for years with some good results, but never with the potency of paclitaxel,” said senior author Dr. Susan Mooberry, professor of pharmacology at the University of Texas Health Science Center. “Now we have that potency, and we also show for the first time the taccalonolides’ cellular binding site. The taccalonolides stabilize microtubules in cancer cells, but they do not attack healthy cells. We have run normal prostate cells and normal breast cells through these tests, and they do not die. The taccalonolides selectively kill cancer cells.”

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