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United States Department of Agriculture

Agricultural Research Service

Research Project: DISCOVERY AND DEVELOPMENT OF NATURAL PRODUCT FOR PHARMACEUTICAL AND AGRICHEMICAL APPLICATIONS Title: Antiparasitic and anticancer carvotacetone derivatives of Sphaeranthus bullatus

Authors
item Machumi, Francis -
item Yenesew, Abiy -
item Midiwo, Jacob -
item Heydenreich, Matthias -
item Kleinpeter, Erich -
item Tekwani, Babu -
item Khan, Shabana -
item Walker, Larry -
item Muhammad, Ilias -

Submitted to: Natural Product Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 15, 2012
Publication Date: September 27, 2012
Citation: Machumi, F., Yenesew, A., Midiwo, J.O., Heydenreich, M., Kleinpeter, E., Tekwani, B.L., Khan, S.I., Walker, L.A., Muhammad, I. 2012. Antiparasitic and anticancer carvotacetone derivatives of Sphaeranthus bullatus. Natural Product Communications. 7(9):1123-1126.

Interpretive Summary: The aerial parts of Sphaeranthus bullatus, an annual herb native to tropical East Africa, have been subjected to phytochemical analysis for the purpose of isolating secondary metabolites and determining the antiplasmodial, antileishmanial and anticancer activities of the isolates. A total of 17 compounds have been isolated with four carvotacetone derivatives showing antiplasmodial activity of IC50 between 0.60-3.40 µg/mL against chloroquine sensitive D6 and chloroquine resistant W2 strains of P. falciparum; antileishmanial activity of IC50 0.70-17.0 µg/mL against L. donovanii promastigotes; and anticancer activity of IC50 <1.1 - 5.3 µg/mL against human tumor cells of SK-MEL, KB, BT-549 and SK-OV-3 for three carvotacetone derivatives. This appears to be the first encounter of antiplamodial, antileishmanial and anticancer activities on carvotacetone derivatives as well as the first report of 3-acetoxy-7-hydroxy-5-tigloyloxycarvotacetone (1) from Sphaeranthus bullatus and the first report of 5-O-ß-glucopyranosylcarvotacetone (5) from the genus sphaeranthus.

Technical Abstract: The CH2Cl2-MeOH (1:1) extract of the aerial parts of Sphaeranthus bullatus, an annual herb native to tropical East Africa, showed activity against chloroquine sensitive D6 (IC50 9.7 µg/ml) and chloroquine resistant W2 (IC50 15.0 µg/ml) strains of P. falciparum. Seventeen secondary metabolites were isolated from the extract through conventional chromatographic techniques and identified using various spectroscopic methods. The compounds were evaluated for their in vitro antiplasmodial, antileishmanial and anticancer activities revealing activity on four carvotacetone derivatives, namely 3-acetoxy-7-hydroxy-5-tigloyloxycarvotacetone (1), 3,7-dihydroxy-5-tigloyloxycarvotacetone (2), 3-acetoxy-5,7-dihydroxycarvotacetone (3) and 3,5,7-trihydroxycarvotacetone (4); with antiplasmodial activity of IC50 1.40, 0.79, 0.60 and 3.40 µg/mL respectively against chloroquine sensitive D6 strains of P. falciparum; antiplasmodial activity of IC50 2.00, 0.90, 0.68 and 2.80 µg/mL respectively against chloroquine resistant W2 strains of P. falciparum; antileishmanial activity of IC50 0.70, 3.00, 0.70 and 17.00 µg/mL respectively against the parasite L. donovanii promastigotes, and anticancer activity against human tumor cells of SK-MEL, KB, BT-549 and SK-OV-3 with IC50 between <1.1 - 5.3 µg/mL for 1-3. In addition, cytotoxic effects of the active compounds were evaluated against monkey kidney fibroblasts (VERO) and pig kidney epithelial cells (LLC-PK11) cells. The structures of carvotacetone derivatives were determined by 1D and 2D NMR spectroscopy, of which the absolute stereochemical configuration of 3-acetoxy-7-hydroxy-5-tigloyloxycarvotacetone (1) was determined as 3R, 4R, 5S by Circular Dichroism, specific rotation, 1H NMR and 2D NMR ROESY and NOESY experiments.

Last Modified: 10/24/2014
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