title: Discovery of novel inhibitors targeting enoyl-acyl carrier protein reductase in Plasmodium falciparum by structure-based virtual screening.
abstract: There is a dire need for novel therapeutics to treat the virulent malarial parasite, Plasmodium falciparum. Recently, the X-ray crystal structure of enoyl-acyl carrier protein reductase (ENR) in complex with triclosan has been determined and provides an opportunity for the rational design of novel inhibitors targeting the active site of ENR. Here, we report the discovery of several compounds by virtual screening and their experimental validation as high potency PfENR inhibitors.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, TPC-28, La Jolla, CA 92037, USA.
authors.forename: George
authors.initials: G
authors.lastname: Nicola
authors.forename: Colin A
authors.initials: CA
authors.lastname: Smith
authors.forename: Edinson
authors.initials: E
authors.lastname: Lucumi
authors.forename: Mack R
authors.initials: MR
authors.lastname: Kuo
authors.forename: Luchezar
authors.initials: L
authors.lastname: Karagyozov
authors.forename: David A
authors.initials: DA
authors.lastname: Fidock
authors.forename: James C
authors.initials: JC
authors.lastname: Sacchettini
authors.forename: Ruben
authors.initials: R
authors.lastname: Abagyan
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D018938:Caco-2 Cells; D018360:Crystallography, X-Ray; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors*; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D008288:Malaria / Q000188:drug therapy; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000201:enzymology*; D014260:Triclosan / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D014260:Triclosan; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)