Proceedings of the National Academy of Sciences - PNAS, 2001-01, Vol.98 (1), p.60-62
2001
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Details
- Autor(en) / Beteiligte
- Titel
- An Anthelmintic Compound, Nafuredin, Shows Selective Inhibition of Complex I in Helminth Mitochondria
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2001-01, Vol.98 (1), p.60-62
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2001
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.011524698Titel-ID: cdi_proquest_miscellaneous_17751015
- Format
- –
- Schlagworte
- Administration, Oral, Animals, Anthelmintics, Anthelmintics - administration & dosage, Anthelmintics - chemistry, Anthelmintics - pharmacology, Anthelmintics - therapeutic use, Ascaris suum - drug effects, Ascaris suum - enzymology, Aspergillus niger, Aspergillus niger - chemistry, Biochemistry, Biological Sciences, Cancer, Chemotherapy, Eggs, Electron Transport - drug effects, Electrons, Energy metabolism, Feces - parasitology, fumarate reductase (NADH), Haemonchiasis - drug therapy, Haemonchus - drug effects, Haemonchus - enzymology, Haemonchus contortus, Infections, Inhibitory Concentration 50, Kinetics, Mitochondria, Mitochondria - drug effects, Mitochondria - enzymology, Molecular Structure, nafuredin, Oxidoreductases - antagonists & inhibitors, Oxidoreductases - metabolism, Oxidoreductases Acting on CH-CH Group Donors, Parasite hosts, Parasites, Parasitism, Pharmaceuticals, Pyrones - administration & dosage, Pyrones - chemistry, Pyrones - pharmacology, Pyrones - therapeutic use, sheep, Sheep - parasitology, Time Factors, Ubiquinone - analogs & derivatives, Ubiquinone - metabolism