dc.contributor.author |
Pillay, P
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dc.contributor.author |
Vleggaar, R
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dc.contributor.author |
Maharaj, VJ
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dc.contributor.author |
Smith, PJ
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dc.contributor.author |
Lategan, CA
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dc.contributor.author |
Chouteau, F
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dc.contributor.author |
Chibale, K
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dc.date.accessioned |
2007-07-02T07:13:46Z |
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dc.date.available |
2007-07-02T07:13:46Z |
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dc.date.issued |
2007-02 |
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dc.identifier.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 |
en |
dc.identifier.issn |
0031-9422 |
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dc.identifier.uri |
http://hdl.handle.net/10204/832
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dc.description |
http://www.sciencedirect.com/science?_ob=PublicationURL&_tockey |
en |
dc.description.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. |
en |
dc.language.iso |
en |
en |
dc.publisher |
Pergamon-Elsevier Science Ltd |
en |
dc.subject |
Vernonia staehelinoides |
en |
dc.subject |
Hirsutinolides |
en |
dc.subject |
Antiplasmodial activity |
en |
dc.subject |
Cytotoxicity |
en |
dc.subject |
Pharmacophores |
en |
dc.subject |
2(5H)-furanone |
en |
dc.subject |
Mucochloric acids |
en |
dc.subject |
Mucobromic acids |
en |
dc.subject |
Malaria |
en |
dc.title |
Antiplasmodial hirsutinolides from Vernonia staehelinoides and their utilization towards a simplified pharmacophore |
en |
dc.type |
Article |
en |
dc.identifier.apacitation |
Pillay, P., Vleggaar, R., Maharaj, V., Smith, P., Lategan, C., Chouteau, F., & Chibale, K. (2007). Antiplasmodial hirsutinolides from Vernonia staehelinoides and their utilization towards a simplified pharmacophore. http://hdl.handle.net/10204/832 |
en_ZA |
dc.identifier.chicagocitation |
Pillay, P, R Vleggaar, VJ Maharaj, PJ Smith, CA Lategan, F Chouteau, and K Chibale "Antiplasmodial hirsutinolides from Vernonia staehelinoides and their utilization towards a simplified pharmacophore." (2007) http://hdl.handle.net/10204/832 |
en_ZA |
dc.identifier.vancouvercitation |
Pillay P, Vleggaar R, Maharaj V, Smith P, Lategan C, Chouteau F, et al. Antiplasmodial hirsutinolides from Vernonia staehelinoides and their utilization towards a simplified pharmacophore. 2007; http://hdl.handle.net/10204/832. |
en_ZA |
dc.identifier.ris |
TY - Article
AU - Pillay, P
AU - Vleggaar, R
AU - Maharaj, VJ
AU - Smith, PJ
AU - Lategan, CA
AU - Chouteau, F
AU - Chibale, K
AB - 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.
DA - 2007-02
DB - ResearchSpace
DP - CSIR
KW - Vernonia staehelinoides
KW - Hirsutinolides
KW - Antiplasmodial activity
KW - Cytotoxicity
KW - Pharmacophores
KW - 2(5H)-furanone
KW - Mucochloric acids
KW - Mucobromic acids
KW - Malaria
LK - https://researchspace.csir.co.za
PY - 2007
SM - 0031-9422
T1 - Antiplasmodial hirsutinolides from Vernonia staehelinoides and their utilization towards a simplified pharmacophore
TI - Antiplasmodial hirsutinolides from Vernonia staehelinoides and their utilization towards a simplified pharmacophore
UR - http://hdl.handle.net/10204/832
ER -
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en_ZA |