Trypanosoma cruzi CYP51 inhibitor derived from a Mycobacterium tuberculosis screen hit.

ABSTRACT:

Background

The two front-line drugs for chronic Trypanosoma cruzi infections are limited by adverse side-effects and declining efficacy. One potential new target for Chagas' disease chemotherapy is sterol 14alpha-demethylase (CYP51), a cytochrome P450 enzyme involved in biosynthesis of membrane sterols.

Methodology/principal finding

In a screening effort targeting Mycobacterium tuberculosis CYP51 (CYP51(Mt)), we previously identified the N-[4-pyridyl]-formamide moiety as a building block capable of delivering a variety of chemotypes into the CYP51 active site. In that work, the binding modes of several second generation compounds carrying this scaffold were determined by high-resolution co-crystal structures with CYP51(Mt). Subsequent assays against the CYP51 orthologue in T

SUBMITTER: Chen CK 

PROVIDER: S-EPMC2629123 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature