Planta Med 2013; 79 - PN70
DOI: 10.1055/s-0033-1348751

Novel Retro-Chalcone Derivatives Isolated from Tacca chantrieri

J Peng 1, 2, AL Risinger 1, 2, G Fest 1, DE Frantz 3, SL Mooberry 1, 2
  • 1Department of Pharmacology
  • 2Cancer Therapy & Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA
  • 3Department of Chemistry, University of Texas at San Antonio, San Antonio, Texas 78249

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.