The role of molecular modeling in the design of analogues of the fungicidal natural products crocacins A and D.

ABSTRACT: Extensive molecular modeling based on crystallographic data was used to aid the design of synthetic analogues of the fungicidal naturally occurring respiration inhibitors crocacins A and D, and an inhibitor binding model to the mammalian cytochrome bc(1) complex was constructed. Simplified analogues were made which showed high activity in a mitochondrial beef heart respiration assay, and which were also active against certain plant pathogens in glasshouse tests. A crystal structure was obtained of an analogue of crocacin D bound to the chicken heart cytochrome bc(1) complex, which validated the binding model and which confirmed that the crocacins are a new class of inhibitor of the cytochrome bc(1) complex.

SUBMITTER: Crowley PJ 

PROVIDER: S-EPMC2784635 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature