Binding mode and potency of N-indolyloxopyridinyl-4-aminopropanyl-based inhibitors targeting Trypanosoma cruzi CYP51.

ABSTRACT: Chagas disease is a chronic infection in humans caused by Trypanosoma cruzi and manifested in progressive cardiomyopathy and/or gastrointestinal dysfunction. Limited therapeutic options to prevent and treat Chagas disease put 8 million people infected with T. cruzi worldwide at risk. CYP51, involved in the biosynthesis of the membrane sterol component in eukaryotes, is a promising drug target in T. cruzi. We report the structure-activity relationships (SAR) of an N-arylpiperazine series of N-indolyloxopyridinyl-4-aminopropanyl-based inhibitors designed to probe the impact of substituents in the terminal N-phenyl ring on binding mode, selectivity and potency. Depending on the substituents at C-4, two distinct ring binding modes, buried and solvent-exposed, have been observed by X-ray struct

SUBMITTER: Vieira DF 

PROVIDER: S-EPMC4266343 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature