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Celastrol inhibits Plasmodium falciparum enoyl-acyl carrier protein reductase.

ABSTRACT: Enoyl-acyl carrier protein reductase (ENR), a critical enzyme in type II fatty acid biosynthesis, is a promising target for drug discovery against hepatocyte-stage Plasmodium falciparum. In order to identify PfENR-specific inhibitors, we docked 70 FDA-approved, bioactive, and/or natural product small molecules known to inhibit the growth of whole-cell blood-stage P. falciparum into several PfENR crystallographic structures. Subsequent in vitro activity assays identified a noncompetitive low-micromolar PfENR inhibitor, celastrol, from this set of compounds.

SUBMITTER: Tallorin LC

PROVIDER: S-EPMC4807855 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Celastrol inhibits Plasmodium falciparum enoyl-acyl carrier protein reductase.

Tallorin Lorillee C LC Durrant Jacob D JD Nguyen Quynh G QG McCammon J Andrew JA Burkart Michael D MD

Bioorganic & medicinal chemistry 20140915 21

Enoyl-acyl carrier protein reductase (ENR), a critical enzyme in type II fatty acid biosynthesis, is a promising target for drug discovery against hepatocyte-stage Plasmodium falciparum. In order to identify PfENR-specific inhibitors, we docked 70 FDA-approved, bioactive, and/or natural product small molecules known to inhibit the growth of whole-cell blood-stage P. falciparum into several PfENR crystallographic structures. Subsequent in vitro activity assays identified a noncompetitive low-micr ...[more]

PMID: 25284249

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