An anthelmintic compound, nafuredin, shows selective inhibition of complex I in helminth mitochondria
AUTOR(ES)
Ōmura, Satoshi
FONTE
The National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=14544Documentos Relacionados
- ER-27319, an acridone-related compound, inhibits release of antigen-induced allergic mediators from mast cells by selective inhibition of Fcɛ receptor I-mediated activation of Syk
- Synthesis of an opine-like compound, a rhizopine, in alfalfa nodules is symbiotically regulated.
- Effect of an oral gold compound, auranofin, on non-specific bronchial hyperresponsiveness in mild asthma.
- Measurement of the cross linking compound, pyridinoline, in urine as an index of collagen degradation in joint disease.
- Inhibition of selective signaling events in natural killer cells recognizing major histocompatibility complex class I.