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.
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Authors | Nils Germonprez, Louis Maes, Luc Van Puyvelde, Mai Van Tri, Duong Anh Tuan, Norbert De Kimpe |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 48
Issue 1
Pg. 32-7
(Jan 13 2005)
ISSN: 0022-2623 [Print] United States |
PMID | 15633999
(Publication Type: Journal Article)
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Chemical References |
- Antiprotozoal Agents
- Saponins
- Triterpenes
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Topics |
- Animals
- Antiprotozoal Agents
(chemistry, pharmacology)
- Drug Evaluation, Preclinical
(methods)
- Humans
- Inhibitory Concentration 50
- Leishmania infantum
(drug effects)
- Leishmaniasis, Visceral
(drug therapy)
- Liver
(drug effects, parasitology)
- Male
- Mice
- Mice, Inbred BALB C
- Molecular Structure
- Plants, Medicinal
(chemistry)
- Saponins
(chemistry, pharmacology)
- Structure-Activity Relationship
- Triterpenes
(chemistry)
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