Planta Med 2013; 79 - PN4
DOI: 10.1055/s-0033-1348685

A Cytotoxic Dimeric Furanoheliangolide from Piptocoma rufescens and Confirmation of the Absolute Configuration of Goyazensolide by Single-Crystal X-Ray Analysis

Y Ren 1, F Jiménez 2, R García 2, M Mejía 2, H Chai 1, FR Fronczek 3, JC Gallucci 4, NR Farnsworth 5, DD Soejarto 5, AD Kinghorn 1
  • 1Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy
  • 4Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210
  • 2Jardín Botánico Nacional “Dr. Rafael Ma. Moscoso”, Santo Domingo, Dominican Republic
  • 3Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803
  • 5Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612

Piptocoma is a small genus of the plant family Asteraceae, of which members grow in tropical and sub-tropical regions of the Western Hemisphere. As part of a search for new natural product anticancer agents from diverse organisms, a leaf crude methanol extract of P. rufescens Cass., collected in the Dominican Republic, was found to be cytotoxic toward the HT-29 human colon cancer cell line. Using column chromatography guided by cytotoxicity to HT-29 cells, a novel dimeric sesquiterpene lactone was isolated from the leaves of P. rufescens. The structure of this novel compound was established from its IR, UV, NMR, and mass spectra, and the absolute configuration was determined by comparison of its CD spectrum with that of goyazensolide, for which the absolute configuration has been established by single-crystal X-ray diffraction using copper radiation. The biogenesis of this dimer was proposed by introduction of an ene reaction, and the cytotoxicity test toward human colon cancer HT-29 cells showed that this compound was highly cytotoxic with an IC50 value of 0.15µM, and was more potent than its monomer, 15-deoxygoyazensolide (IC50, 0.26µM). This study describes the first dimeric furanoheliangolide, a highly cytotoxic compound showing potential for further study as a new anticancer drug lead.