The antileishmanial activity of novel oxygenated chalcones and their mechanism of action

Our previous studies have shown that licochalcone A, an oxygenated chalcone, has antileishmanial and antimalarial activities, and alters the ultrastructure and function of the mitochondria of Leishmania spp. parasites. The present study was designed to investigate the antileishmanial activity and th...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 1999-06, Vol.43 (6), p.793-803
Main Authors: LIN ZHAI, MING CHEN, BLOM, J, THEANDER, T. G, CHRISTENSEN, S. B, KHARAZMI, A
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiparasitic agents
Antiprotozoal Agents - chemistry
Antiprotozoal Agents - pharmacology
Antiprotozoal Agents - therapeutic use
Biological and medical sciences
Chalcone - chemistry
Chalcone - pharmacology
Chalcone - therapeutic use
Cricetinae
Drug Evaluation, Preclinical
Humans
Leishmania donovani
Leishmania donovani - drug effects
Leishmania donovani - growth & development
Leishmania donovani - ultrastructure
Leishmania major
Leishmania major - drug effects
Leishmania major - growth & development
Leishmania major - ultrastructure
Leishmaniasis, Cutaneous - drug therapy
Leishmaniasis, Visceral - drug therapy
Macrophages - drug effects
Macrophages - parasitology
Male
Medical sciences
Mesocricetus
Mitochondria - drug effects
Mitochondria - enzymology
Mitochondria - ultrastructure
Oxidoreductases - drug effects
Oxidoreductases - metabolism
Pharmacology. Drug treatments
Respiration - drug effects
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Summary:Our previous studies have shown that licochalcone A, an oxygenated chalcone, has antileishmanial and antimalarial activities, and alters the ultrastructure and function of the mitochondria of Leishmania spp. parasites. The present study was designed to investigate the antileishmanial activity and the mechanism of action of a group of new oxygenated chalcones. The tested oxygenated chalcones inhibited the in-vitro growth of Leishmania major promastigotes and Leishmania donovani amastigotes. Treatment of hamsters infected with L. donovani with intraperitoneal administration of two oxygenated chalcones resulted in a significant reduction of parasite load in the liver and the spleen compared with untreated control animals. The oxygenated chalcones also inhibited the respiration of the parasite and the activity of mitochondrial dehydrogenases. Electron microscopic studies illustrated that they altered the ultrastructure of the mitochondria of L. major promastigote. The data clearly indicate that this group of oxygenated chalcones has a strong antileishmanial activity and might be developed into a new antileishmanial drug. The antileishmanial activity of oxygenated chalcones might be the result of interference with function of the parasite mitochondria.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/43.6.793