Nafuredin was isolated from Aspergillus niger which is marine strain. It inhibits NADH-fumarate reductase of anaerobic electron transport system in helminth mitochondria. Moreover, nafuredin exerts anthelmintic activity against Haemonchus contortus in in vivo trials with sheep.
Origin:Trichoderma harzianum.
CAS Registry Number: 224427-79-6
CA Index Name: (1R,2R,5R,6S)-5-Hydroxy-1-methyl2-[(1E,3E,5R,7E,9E,11S)-5,7,11- trimethyltrideca-1,3,7,9-tetraenyl]- 3,7-dioxabicyclo[4.1.0]heptane-4- one
Handling and Storage: Store at -20℃. Do not dry up.
Relevance in Human Disease
Treatment of Helminth Infections: Helminth infections, such as those caused by Haemonchus contortus, are significant health problems globally. Nafuredin's ability to selectively inhibit helminth mitochondrial enzymes makes it a promising candidate for developing new anthelmintic drugs.
Potential Impact on Immune Response: Helminth infections can impair the host's immune response to other diseases, such as HIV and tuberculosis. By effectively treating helminth infections, nafuredin may indirectly help improve immune responses to these diseases.
Addressing Drug Resistance: The emergence of resistance to existing anthelmintics necessitates the development of new drugs. Nafuredin offers a novel mechanism of action that could be effective against resistant strains of helminths.
Cell Signaling Pathway
Nafuredin is primarily associated with the inhibition of specific electron transport pathways in helminth mitochondria. The key pathway related to nafuredin is the NADH-fumarate reductase system, which is unique to anaerobic energy metabolism in helminths. This system includes:
Complex I (NADH-rhodoquinone reductase): Nafuredin inhibits this complex by competing for the quinone-binding site, which is crucial for electron transport in helminth mitochondria.
Complex II (rhodoquinol-fumarate reductase): Although nafuredin primarily targets Complex I, it also affects Complex II as part of the NADH-fumarate reductase system.
These pathways are essential for the anaerobic energy metabolism of helminths, allowing them to generate ATP in low-oxygen environments. Nafuredin's inhibition of these pathways disrupts the energy production in parasites, contributing to its anthelmintic activity.