+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Effects of ketoconazole on sterol biosynthesis by Trypanosoma cruzi epimastigotes



Effects of ketoconazole on sterol biosynthesis by Trypanosoma cruzi epimastigotes



Biochemical and Biophysical Research Communications 1363: 851-856



Reproduction of Trypanosoma cruzi epimastigotes in a liver infusion-tryptose-serum medium was inhibited by the antimycotic agent ketoconazole. Effective drug concentrations also blocked the biosynthesis of the parasite's fungal-type sterols at the stage of C-14 demethylation, as demonstrated by radioisotopic, chromatographic and mass spectrometric methods. Coincidently, a 4,4,14 alpha-trimethyl sterol, 24-methylenedihydrolanosterol, accumulated and came to replace as much as three fourths of the free sterol content of the cells. Precedents from studies with fungi are invoked to suggest that the cytotoxicity of ketoconazole for T. cruzi is a consequence of the inability of 24-methylenedihydrolanosterol to perform the membrane lipid bilayer functions of the normal epimastigote sterols.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 001353291

Download citation: RISBibTeXText

PMID: 3521598

DOI: 10.1016/0006-291x(86)90410-9


Related references

Ketoconazole alters sterol biosynthesis by trypanosoma cruzi epimastigotes. Abstracts of the Annual Meeting of the American Society for Microbiology 86: 24, 1986

Concentration and time dependence of the effects of ketoconazole on growth and sterol synthesis by trypanosoma cruzi epimastigotes. Acta Cientifica Venezolana 39(2): 140-146, 1988

Modification of the sterol composition of Trypanosoma cruzi epimastigotes by DELTA-24 -sterol methyltransferase inhibitors and their combinations with ketoconazole. Molecular & Biochemical Parasitology 73(1-2): 199-210, 1995

Modification of the sterol composition of Trypanosoma (Schizotrypanum) cruzi epimastigotes by 24(25)-sterol methyl transferase inhibitors and their combinations with ketoconazole. Molecular and Biochemical Parasitology 73(1-2): 199-210, 1995

Modification of the sterol composition of Trypanosoma (Schizotrypanum) cruzi epimastigotes by delta 24(25)-sterol methyl transferase inhibitors and their combinations with ketoconazole. Molecular and Biochemical Parasitology 73.1-2: 199-210, 1995

Modification of the sterol composition of Trypanosoma cruzi epimastigotes by sterol biosynthesis inhibitors leads to profound changes of the membrane phospholipids through inhibition of the phosphatidylethanolamine-phosphatidylcholine-N-methyl-transferase. Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 35: 58, 1995

Ultrastructural alterations induced by two ergosterol biosynthesis inhibitors ketoconazole and terbinafine on epimastigotes and amastigotes of trypanosoma cruzi. Antimicrobial Agents & Chemotherapy 34(11): 2097-2105, 1990

Ultrastructural alterations induced by two ergosterol biosynthesis inhibitors, ketoconazole and terbinafine, on epimastigotes and amastigotes of Trypanosoma (Schizotrypanum) cruzi. Antimicrobial Agents and ChemoTherapy 34(11): 2097-2105, 1990

Synergistic effects of ketoconazole and SF-86327 on the proliferation of epimastigotes and amastigotes of Trypanosoma (Schizotrypanum) cruzi. Annals of the New York Academy of Sciences 544: 357-358, 1988

Altered lipid composition and enzyme activities of plasma membranes from Trypanosoma (Schizotrypanum) cruzi epimastigotes grown in the presence of sterol biosynthesis inhibitors. Biochemical Pharmacology 53(5): 697-704, 1997

Effects of inhibitors of Delta24(25)-sterol methyl transferase on the ultrastructure of epimastigotes of Trypanosoma cruzi. Microscopy and Microanalysis 11(6): 506-515, 2005

Mechanism of action of anti-proliferative lysophospholipid analogues against the protozoan parasite Trypanosoma cruzi: potentiation of in vitro activity by the sterol biosynthesis inhibitor ketoconazole. Journal of Antimicrobial ChemoTherapy 47(5): 537-546, 2001

Antiproliferative synergism of the allylamine SF 86-327 and ketoconazole on epimastigotes and amastigotes of Trypanosoma (Schizotrypanum) cruzi. Antimicrobial Agents and ChemoTherapy 32(8): 1237-1242, 1988

Alteration of lipid order profile and permeability of plasma membranes from Trypanosoma cruzi epimastigotes grown in the presence of ketoconazole. Molecular and Biochemical Parasitology 302: 185-195, 1988

Upregulation of sterol C14-demethylase expression in Trypanosoma cruzi treated with sterol biosynthesis inhibitors. Molecular and Biochemical Parasitology 144(1): 68-75, 2005