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Interactions of antiparasitic sterols with sterol 14?-demethylase (CYP51) of human pathogens.

ABSTRACT: Sterol 14?-demethylase is a validated and an attractive drug target in human protozoan parasites. Pharmacological inactivation of this important enzyme has proven very effective against fungal infections, and it is a target that is being exploited for new antitrypanosomal and antileishmanial chemotherapy. We have used in silico calculations to identify previously reported antiparasitic sterol-like compounds and their structural congeners that have preferential and high docking affinity for CYP51. The sterol 14?-demethylase from Trypanosoma cruzi and Leishmania infantum, in particular, preferentially dock to taraxerol, epi-oleanolic acid, and ?/?-amyrim structural scaffolds. These structural information and predicted interactions can be exploited for fragment/structure-based antiprotozoal drug design.

SUBMITTER: Warfield J

PROVIDER: S-EPMC4410773 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Interactions of antiparasitic sterols with sterol 14α-demethylase (CYP51) of human pathogens.

Warfield Jasmine J Setzer William N WN Ogungbe Ifedayo Victor IV

SpringerPlus 20141120

Sterol 14α-demethylase is a validated and an attractive drug target in human protozoan parasites. Pharmacological inactivation of this important enzyme has proven very effective against fungal infections, and it is a target that is being exploited for new antitrypanosomal and antileishmanial chemotherapy. We have used in silico calculations to identify previously reported antiparasitic sterol-like compounds and their structural congeners that have preferential and high docking affinity for CYP51 ...[more]

PMID: 25932361

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