Discovery of novel inhibitors targeting enoyl-acyl carrier protein reductase in Plasmodium falciparum by structure-based virtual screening.
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.
Nicola
George
G
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, TPC-28, La Jolla, CA 92037, USA.
Smith
Colin A
CA
Lucumi
Edinson
E
Kuo
Mack R
MR
Karagyozov
Luchezar
L
Fidock
David A
DA
Sacchettini
James C
JC
Abagyan
Ruben
R
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
D000962:Antimalarials; D014260:Triclosan; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)