AN ANTIBIOTIC, ASCOFURANONE, SPECIFICALLY INHIBITS RESPIRATION AND IN-VITRO GROWTH OF LONG SLENDER BLOOD-STREAM FORMS OF TRYPANOSOMA-BRUCEI-BRUCEI (VOL 81, PG 127, 1996)

Ascofuranone, a prenylphenol antibiotic isolated from a phytopathogeni c fungus, Ascochyta visiae, strongly inhibited both glucose-dependent cellular respiration and glycerol-3-phosphate-dependent mitochondrial O-2 consumption of long slender bloodstream forms of Trypanosoma bruce i brucei. This inhibition was suggested to be due to inhibition of the mitochondrial electron-transport system, composed of glycerol-3-phosp hate dehydrogenase (EC 1.1.99.5) and plant-like alternative oxidase. A scofuranone noncompetitively inhibited the reduced coenzyme Q(1)-depen dent O-2 uptake of the mitochondria with respect to ubiquinol (K-i = 2 .38 nM). Therefore, the susceptible site is deduced to be the ubiquino ne redox machinery which links the two enzyme activities. Further, asc ofuranone in combination with glycerol completely blocked energy produ ction, 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. (C) 1997 Else vier Science B.V.