title: In vitro and in vivo anti-leishmanial activity of triterpenoid saponins isolated from Maesa balansae and some chemical derivatives.
abstract: 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.
authors.affiliation: Tibotec nv, Generaal De Wittelaan 11 bus 4, B-2800 Mechelen, Belgium.
authors.forename: Nils
authors.initials: N
authors.lastname: Germonprez
authors.forename: Louis
authors.initials: L
authors.lastname: Maes
authors.forename: Luc
authors.initials: L
authors.lastname: Van Puyvelde
authors.forename: Mai
authors.initials: M
authors.lastname: Van Tri
authors.forename: Duong Anh
authors.initials: DA
authors.lastname: Tuan
authors.forename: Norbert
authors.initials: N
authors.lastname: De Kimpe
mesh_terms: 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
chemical_list: D000981:Antiprotozoal Agents; D012503:Saponins; D014315:Triterpenes