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Please use this identifier to cite or link to this item: http://hdl.handle.net/10204/832

Title: Antiplasmodial hirsutinolides from Vernonia staehelinoides and their utilization towards a simplified pharmacophore
Authors: Pillay, P
Vleggaar, R
Maharaj, VJ
Smith, PJ
Lategan, CA
Chouteau, F
Chibale, K
Keywords: Vernonia staehelinoides
Hirsutinolides
Antiplasmodial activity
Cytotoxicity
Pharmacophores
2(5H)-furanone
Mucochloric acids
Mucobromic acids
Malaria
Issue Date: Feb-2007
Publisher: Pergamon-Elsevier Science Ltd
Citation: Pillay, P et al. 2007. Antiplasmodial hirsutinolides from Vernonia staehelinoides and their utilization towards a simplified pharmacophore. Phytochemistry, Vol. 68(8) pp 1200-1205
Abstract: The dichloromethane extract of the leaves of Vernonia staehelinoides Harv. (Asteraceae) showed in vitro activity (IC50 ~3 µg/ml) against the chloroquine-sensitive (D10) and the chloroquine-resistant (K1) strains of Plasmodium falciparum. Through conventional chromatographic techniques and bioassay-guided fractionation two structurally-related hirsutinolides displaying in vitro antiplasmodial activity (IC50 -0.2 µg/ml against D10) were isolated and identified by spectroscopic data. Compounds 1, 8a-(2-methylacryloyloxy)-3-oxo-1-desoxy-1,2-dehydrohirsutinolide-13-O-acetate, and 2, 8a-(5'-acetoxysenecioyloxy)-3-oxo-1-desoxy-1,2-dehydrohirsutinolide-13-O-acetate were found to be cytotoxic to mammalian Chinese Hamster Ovarian (CHO) cells at similar concentrations but proved to be attractive scaffolds for structure-activity relationship studies. Two main privileged substructures, a 2(5H)-furanone unit and a dihydrofuran-4-one unit, were identified as potential pharmacophores which may be responsible for the observed biological activity. In order to verify this, mucochloric and mucobromic acids were selected as appropriate 2(5H)-furanone substructures and these were shown to have comparable activity against the D10 and superior activity against the K1 strains relative to the hirsutinolide natural product. Mucochloric and mucobromic acids also show selective cytotoxicity to the malaria parasites compared to mammalian (CHO) cells in vitro. The antiplasmodial data obtained in respect of these two acids suggests that the 2(5H)-furanone substructure is a key pharmacophore in the observed antiplasmodial activity.
Description: http://www.sciencedirect.com/science?_ob=PublicationURL&_tockey
URI: http://hdl.handle.net/10204/832
ISSN: 0031-9422
Appears in Collections:Plant biotechnology
General science, engineering & technology

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