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Journal of Antimicrobial Chemotherapy (1999) 43, 793-803
© 1999 The British Society for Antimicrobial Chemotherapy

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

Lin Zhaia,b, Ming Chena,b, Jens Blomb, Thor G. Theanderc, Søren Brøgger Christensend and Arsalan Kharazmi*,a

a Centre for Medical Parasitology, Department of Clinical Microbiology, University Hospital (Rigshospitalet), Copenhagen, Denmark b Department of Molecular Cell Biology, Institute for Medical Microbiology and Immunology, Copenhagen University, Copenhagen, Denmark c Statens Serum Institut, Institute for Medical Microbiology and Immunology, Copenhagen University, Copenhagen, Denmark d Department of Medicinal Chemistry, The Royal Danish School of Pharmacy, Copenhagen, Denmark

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.

* Correspondence address. Department of Clinical Microbiology, Rigshospitalet 7806, Tagensvej 20, DK-2200 Copenhagen, Denmark. Tel: +45-35-45-77-34; Fax: +45-35-45-68-31; E-mail: Kharazmi{at}inet.uni2.dk


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