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Novel Retro-Chalcone Derivatives Isolated from Tacca chantrieri
Plants of the genus Tacca have yielded a diverse range of molecules, including glycosides, diarylheptanoids, saponins, withanolides, the taccalonolides and a cytotoxic benzoquinone-type retro-dihydrochalcone named evelynin. In the current study, we identified 6 additional retro-dyhydrochalcones from Tacca chantrieri, named taccabulin A – E and evelynin B. Bioassays of these compounds identified that taccabulin A has the ability to depolymerize cellular microtubules and inhibit the proliferation of the MDA-MB-435 melanoma cells with an IC50 of 435 nM. This activity was confirmed with a two-step total synthesis of taccabulin A. This is the first report of a microtubule destabilizer isolated from Tacca sp., which also produce the taccalonolide class of microtubule stabilizers. This finding is particularly intriguing due to the fact that the ability of a single natural source to produce both classes, microtubule stabilizers and destabilizers, is unprecedented. Evelynin B also showed antiproliferative activity with an IC50 of 10µM but no indication of microtubule specific activity. Taccabulins B, C, D and E showed no antiproliferative effects at concentrations as high as 10µM. The isolation and biological characterization of several retro-dihydrochalcones from Tacca chantrieri allows for preliminary structure activity relationships to be made for this compound class for both antiproliferative and microtubule depolymerizing activities.