In vitro and in vivo anti-leishmanial activity of triterpenoid saponins isolated from Maesa balansae and some chemical derivatives.
The methanolic extract from the leaves of the Vietnamese medicinal plant Maesa balansae showed potent in vitro and in vivo activity against the tropical protozoal parasite Leishmania infantum. Bioassay-guided purification of the extract led to the identification of six triterpenoid saponins, maesabalides I-VI (1-6), each having a strong and specific anti-leishmanial activity. Maesabalide III (3) and IV (4) were the most potent with IC(50) values against intracellular amastigotes of about 7 and 14 ng/mL. In comparison, the IC(50) value of sodium stibogluconate, the reference drug for treatment of leishmaniasis, is only 5.6 microg/mL. No cytotoxicity was present on a human fibroblast (MRC-5) cell line (CC(50) > 32 microg/mL). In vivo evaluation in the BALB/C mouse model demonstrated that >90% reduction of liver amastigote burdens was obtained 1 week after a single subcutaneous dose at 0.2-0.4 mg/kg was administered. Several chemical derivatives of maesabalides I-VI were prepared in order to study the structure-activity relationship.
Germonprez
Nils
N
Tibotec nv, Generaal De Wittelaan 11 bus 4, B-2800 Mechelen, Belgium.
Maes
Louis
L
Van Puyvelde
Luc
L
Van Tri
Mai
M
Tuan
Duong Anh
DA
De Kimpe
Norbert
N
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D020128:Inhibitory Concentration 50; D018314:Leishmania infantum / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy; D008099:Liver / Q000187:drug effects / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D012503:Saponins / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry
D000981:Antiprotozoal Agents; D012503:Saponins; D014315:Triterpenes