The antileishmanial agent licochalcone A interferes with the function of parasite mitochondria

Abstract

Our previous studies have shown that licochalcone A, an oxygenated chalcone, has antileishmanial (M. Chen, S.B. Christensen, J. Blom, E. Lemmich, L. Nadelmann, K. Fich, T.G. Theander, and A. Kharazmi, Antimicrob, Agents Chemother. 37:2550-2556, 1993; M. Chen, S.B. Christensen, T.G. Theander, and A. Khrazmi, Antimicrob. Agents Chemother. 38:1339-1344, 1994) and antimalarial (M. Chen, T.G. Theander, S.B. Christensen, L. Hviid, L. Zhai, and A. Kaharazmi, Antimicrob. Agents Chemother. 38:1470-1475, 1994) activities. We have observed that licochalcone A alters the ultrastructure of the mitochondria of Leishmania promastigotes (Chen et al., Antimicrob. Agents Chemother. 37:2550-2556, 1993). The present study was designed to examine this observation further and investigate the mechanism of action of antileishmanial activity of licochalcone A. Electron microscopic studies showed that licochalcone A altered the ultrastructure of Leishmania major promastigote and amastigote mitochondria in a concentration-dependent manner without damaging the organelles of macrophages or the phagocytic function of these cells. Studies on the function of the parasite mitochondria showed that licochalcone A inhibited the respiration of the parasite by the parasites. Moreover, licochalcone A inhibited the activity of the parasite mitochondrial dehydrogenase. The inhibition of the activity of the parasite mitochondrial enzyme correlated well with the changes in the ultrastructure of the mitochondria shown by electron microscopy. These findings demonstrate that licochalcone A alters the ultrastructure and function of the mitochondria of Leishmania parasites.