Oxazolidinones: a new chemical class of fungicides and inhibitors of mitochondrial cytochrome bc 1 function

✍ Scribed by Jordan, Douglas B; Livingston, Robert S; Bisaha, John J; Duncan, Keith E; Pember, Stephen O; Picollelli, Michael A; Schwartz, Rand S; Sternberg, Jeffrey A; Tang, Xiao-Song

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 142 KB
• Volume: 55
• Category: Article
• ISSN: 1526-498X
• DOI: 10.1002/(sici)1096-9063(199902)55:2<213::aid-ps875>3.0.co;2-n

✦ Synopsis

Famoxadone is a preventative and curative fungicide recently commercialized for plantdisease control. The molecule and its oxazolidinone analogs are potent inhibitors of mitochondrial ubiquinol : cytochrome c oxidoreductase (cytochrome and they bind in the site of the bc 1 ) Q 0 enzyme near the low potential heme of cytochrome b. Inhibitor binding constants for üve mutant cytochrome enzymes from Saccharomyces cerevi-bc 1 siae having single amino acid changes in their apocytochrome b located near the low potential heme were compared with their two parental wildtype enzymes. The üve individual amino acid changes altered the inhibition constants for the inhibitors famoxadone, myxothiazol, azoxystrobin, and kresoxim-methyl in dissimilar fashion. The log scale diþ erences in binding constants relative to those of their parentals provide üngerprints for the eþ ects of the amino acid changes on binding of the individual inhibitors, thus reýecting the structural diversity of the inhibitors.