Author/Authors :
Linna Zhou، نويسنده , , Hironori Ishizaki، نويسنده , , Michaela Spitzer، نويسنده , , Kerrie L. Taylor، نويسنده , , Nicholas D. Temperley، نويسنده , , Stephen L. Johnson، نويسنده , , Paul Brear، نويسنده , , Philippe Gautier، نويسنده , , Zhiqiang Zeng، نويسنده , , Amy Mitchell، نويسنده , , Vikram Narayan، نويسنده , , Ewan M. McNeil، نويسنده , , David W. Melton، نويسنده , , TERRY K. SMITH، نويسنده , , Mike Tyers، نويسنده , , Nicholas ، نويسنده ,
Abstract :
Understanding how drugs work in vivo is critical for drug design and for maximizing the potential of currently available drugs. 5-nitrofurans are a class of prodrugs widely used to treat bacterial and trypanosome infections, but despite relative specificity, 5-nitrofurans often cause serious toxic side effects in people. Here, we use yeast and zebrafish, as well as human in vitro systems, to assess the biological activity of 5-nitrofurans, and we identify a conserved interaction between aldehyde dehydrogenase (ALDH) 2 and 5-nitrofurans across these species. In addition, we show that the activity of nifurtimox, a 5-nitrofuran anti-trypanosome prodrug, is dependent on zebrafish Aldh2 and is a substrate for human ALDH2. This study reveals a conserved and biologically relevant ALDH2-5-nitrofuran interaction that may have important implications for managing the toxicity of 5-nitrofuran treatment.
