An antibiotic, ascofuranone, specifically inhibits respiration and in vitro growth of long slender bloodstream forms of Trypanosoma brucei brucei.

Abstract

Ascofuranone, a prenylphenol antibiotic isolated from a phytopathogenic fungus, Ascochyta visiae, strongly inhibited both glucose-dependent cellular respiration and glycerol-3-phosphate-dependent mitochondrial O2 consumption of long slender bloodstream forms of Trypanosoma brucei brucei. This inhibition was suggested to be due to inhibition of the mitochondrial electron-transport system, composed of glycerol-3-phosphate dehydrogenase (EC 1.1.99.5) and plant-like alternative oxidase. Ascofuranone noncompetitively inhibited the reduced coenzyme Q1-dependent O2 uptake of the mitochondria with respect to ubiquinol (Ki = 2.38 nM). Therefore, the susceptible site is deduced to be the ubiquinone redox machinery which links the two enzyme activities. Further, ascofuranone in combination with glycerol completely blocked energy production, and potently inhibited the in vitro growth of the parasite. Our findings suggest that ascofuranone might be a promising candidate for the chemotherapeutic agents of African trypanosomiasis.

• Authors: N Minagawa, Y Yabu, K Kita, K Nagai, N Ohta, K Meguro, S Sakajo, A Yoshimoto
• Journal: Molecular and biochemical parasitology (Mol Biochem Parasitol) Vol. 84 Issue 2 Pg. 271-80 (Feb 1997) ISSN: 0166-6851 [Print] Netherlands
• PMID: 9084049 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Corrected and Republished Article)

Chemical References

• Anti-Bacterial Agents
• Glycerophosphates
• Sesquiterpenes
• Trypanocidal Agents
• Ubiquinone
• alpha-glycerophosphoric acid
• ascofuranone
• Glucose
• Glycerol

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Electron Transport (drug effects)
• Energy Metabolism (drug effects)
• Glucose (metabolism)
• Glycerol (pharmacology)
• Glycerophosphates (metabolism)
• In Vitro Techniques
• Male
• Mice
• Mitochondria (drug effects, metabolism)
• Oxidation-Reduction
• Oxygen Consumption (drug effects)
• Rats
• Rats, Wistar
• Sesquiterpenes (pharmacology)
• Trypanocidal Agents (pharmacology)
• Trypanosoma brucei brucei (drug effects, growth & development, metabolism)
• Trypanosomiasis, African (blood, drug therapy, parasitology)
• Ubiquinone (metabolism)