title: Identification of new antimalarial leads by use of virtual screening against cytochrome bc₁.
abstract: Cytochrome bc(1) is a validated drug target in malaria parasites. The spread of Plasmodium falciparum strains resistant to multiple antimalarials emphasizes the urgent need for new drugs. We screened in silico the ZINC and MOE databases, using ligand- and structure-based approaches, to identify new leads for development. The most active compound presented an IC(50) value against cultured P. falciparum of 2 μM and a docking pose consistent with its activity.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-019 Lisbon, Portugal.
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.forename: Rui
authors.initials: R
authors.lastname: Moreira
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
authors.forename: Paul M
authors.initials: PM
authors.lastname: O Neill
authors.forename: Giancarlo A
authors.initials: GA
authors.lastname: Biagini
authors.forename: Francisca
authors.initials: F
authors.lastname: Lopes
authors.forename: Daniel J V A
authors.initials: DJ
authors.lastname: dos Santos
authors.forename: Rita C
authors.initials: RC
authors.lastname: Guedes
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D016208:Databases, Factual; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008024:Ligands; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology*
chemical_list: D000962:Antimalarials; D004791:Enzyme Inhibitors; D008024:Ligands; D014450:Electron Transport Complex III