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Proc Natl Acad Sci U S A. 2001 Jan 2;98(1):60-2.

An anthelmintic compound, nafuredin, shows selective inhibition of complex I in helminth mitochondria.

Author information

1
Research Center for Biological Function, The Kitasato Institute, Shirokane, Minato-ku, Tokyo 108-8642, Japan. omura-s@kitasato.or.jp

Abstract

Infections with parasitic helminths are important causes of morbidity and mortality worldwide. New drugs that are parasite specific and minimally toxic to the host are needed to counter these infections effectively. Here we report the finding of a previously unidentified compound, nafuredin, from Aspergillus niger. Nafuredin inhibits NADH-fumarate reductase (complexes I + II) activity, a unique anaerobic electron transport system in helminth mitochondria, at nM order. It competes for the quinone-binding site in complex I and shows high selective toxicity to the helminth enzyme. Moreover, nafuredin exerts anthelmintic activity against Haemonchus contortus in in vivo trials with sheep. Thus, our study indicates that mitochondrial complex I is a promising target for chemotherapy, and nafuredin is a potential lead compound as an anthelmintic isolated from microorganisms.

PMID:
11120889
PMCID:
PMC14544
DOI:
10.1073/pnas.011524698
[Indexed for MEDLINE]
Free PMC Article

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