Identification of two new phenathrenones and a saponin as antiprotozoal constituents of Drypetes gerrardii

•HPLC-based activity profiling for targeted discovery of antiprotozoal compounds.•Two new phenanthrenones with high antiplasmodial activity in vitro activity were identified.•A monodesmosidic saponin was responsible for the trypanocidal activity of a MeOH extract. In an in vitro screen of 206 extrac...

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Veröffentlicht in:Phytochemistry letters 2014-12, Vol.10, p.cxxxiii-cxl
Hauptverfasser: Hata, Yoshie, De Mieri, Maria, Ebrahimi, Samad Nejad, Mokoka, Tsholofelo, Fouche, Gerda, Kaiser, Marcel, Brun, Reto, Potterat, Olivier, Hamburger, Matthias
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Sprache:eng
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Zusammenfassung:•HPLC-based activity profiling for targeted discovery of antiprotozoal compounds.•Two new phenanthrenones with high antiplasmodial activity in vitro activity were identified.•A monodesmosidic saponin was responsible for the trypanocidal activity of a MeOH extract. In an in vitro screen of 206 extracts from South African plants, the CH2Cl2/MeOH (1:1) stem extract of Drypetes gerrardii Hutch. var gerrardii (Putranjivaceae) inhibited Plasmodium falciparum and Leishmania donovani (IC50s of 0.50 and 7.31μg/ml, respectively). In addition, the CH2Cl2/MeOH (1:1) extract of the leaves showed activity against Trypanosoma brucei rhodesiense (IC50 of 12.1μg/ml). The active constituents were tracked by HPLC-based activity profiling, and isolated by preparative and semi-preparative RP-HPLC chromatography. Their structures were established by HRESIMS, and 1D and 2D NMR (1H, 13C, COSY, HMBC, HSQC, and NOESY). From the stem extract, a new phenanthrenone derivative, drypetenone D (1), and a phenanthrenone heterodimer, drypetenone E (2), were isolated. Compound 1 showed potent in vitro activity against P. falciparum (IC50 of 0.9μM) with a selectivity index (SI) of 71, as calculated from cytotoxicity data for L-6 cells. These data qualified 1 for in vivo assessment in the Plasmodium berghei mouse model, but the compound turned out to be inactive. Compound 2 also exhibited good in vitro antiplasmodial activity (IC50 of 2.0μM) and selectivity (SI 31). From the leaf extract, the saponin putranoside A (3) was isolated and identified. Compound 3 showed weak in vitro trypanocidal activity, with an IC50 of 18.0μM, and a SI of 4.
ISSN:1874-3900
1876-7486
DOI:10.1016/j.phytol.2014.05.005