Altered sterol profile induced in Leishmania amazonensis by a natural dihydroxymethoxylated chalcone

Objectives The effects of the antileishmanial chalcone 2′,6′-dihydroxy-4′-methoxychalcone (DMC) on Leishmania amazonensis sterol composition and biosynthesis were investigated to obtain information about the mechanism of growth inhibition by DMC on this parasite. Methods The interference of sterol b...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2009-03, Vol.63 (3), p.469-472
Main Authors: Torres-Santos, Eduardo Caio, Sampaio-Santos, Maria Isabel, Buckner, Frederick S., Yokoyama, Kohei, Gelb, Michael, Urbina, Julio A., Rossi-Bergmann, Bartira
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimicrobial agents
Antiprotozoal Agents - pharmacology
Biological and medical sciences
Chalcone - pharmacology
Cholesterol
Chromatography, Thin Layer
Enzyme Inhibitors - pharmacology
Gas Chromatography-Mass Spectrometry
Inhibitor drugs
ketoconazole
Leishmania - chemistry
Leishmania - metabolism
Leishmania amazonensis
lipid metabolism
Lipids
Medical sciences
Metabolism
Original Research
Parasitic diseases
Pharmacology. Drug treatments
Sterols - biosynthesis
Trypanosoma
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Summary:Objectives The effects of the antileishmanial chalcone 2′,6′-dihydroxy-4′-methoxychalcone (DMC) on Leishmania amazonensis sterol composition and biosynthesis were investigated to obtain information about the mechanism of growth inhibition by DMC on this parasite. Methods The interference of sterol biosynthesis by DMC was studied in drug-treated promastigotes by two different methods. (i) Newly synthesized sterols from parasites grown in the presence of [3H]mevalonate were analysed by thin layer chromatography (TLC)/fluorography. (ii) Total sterols extracted from the parasites grown with or without DMC were characterized by gas chromatography coupled to mass spectroscopy (GC/MS). Results TLC and GC/MS analyses of sterols extracted from DMC-treated promastigotes revealed the accumulation of early precursors and a reduction in the levels of C-14 demethylated and C-24 alkylated sterols, as well as a reduction in exogenous cholesterol uptake. Conclusions This study demonstrates that the natural chalcone DMC alters the sterol composition of L. amazonensis and suggests that the parasite target is different from other known sterol inhibitors.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkn546