title: 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.
authors.forename: Lorillee C
authors.initials: LC
authors.lastname: Tallorin
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Durrant
authors.forename: Quynh G
authors.initials: QG
authors.lastname: Nguyen
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
authors.forename: Michael D
authors.initials: MD
authors.lastname: Burkart
mesh_terms: D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000382:microbiology; D062105:Molecular Docking Simulation; D053978:Pentacyclic Triterpenes; D010963:Plasmodium falciparum / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); C050414:celastrol
keywords: Celastrol; Enoyl-acyl carrier protein reductase; Malaria; Plasmodium falciparum; in silico