biostudies-literatureCrowley PJNIDDK NIH HHSNIGMS NIH HHS10345-55https://www.ebi.ac.uk/biostudies/studies/S-EPMC2784635biostudies-literatureUnknown16(24)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.Bioorganic & medicinal chemistryThe role of molecular modeling in the design of analogues of the fungicidal natural products crocacins A and D.PMC2784635R01 DK044842-14R01 GM038237-22R01 DK044842R01 GM038237Daldal FCromartie TViner RGodfrey CRLee DWPhillips JETaylor ACrowley PJBerry EAfalseThe role of molecular modeling in the design of analogues of the fungicidal natural products crocacins A and D.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.2008-01-01T00:00:00Z2008 Dec2025-04-05T15:49:20.408Z2019-03-27T00:26:55ZS-EPMC27846351899670010.1016/j.bmc.2008.10.030