title: Docking studies of structurally diverse antimalarial drugs targeting PfATP6: no correlation between in silico binding affinity and in vitro antimalarial activity.
abstract: PfATP6, a calcium-dependent ATPase of Plasmodium falciparum, is considered the putative target of the antimalarial drug artemisinin and its derivatives. Herein, the 3D structure of PfATP6 was modeled on the basis of the crystal structure of SERCA 1a, the mammalian homologue. Model validation was achieved using protein structure checking tools. AutoDock4 was used to predict the binding affinities of artemisinin (and analogues) and various other antimalarial agents for PfATP6, for which in vitro activity is also reported. No correlation was found between the affinity of the compounds for PfATP6 predicted by AutoDock4 and their antimalarial activity.
authors: CNRS-LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, 31077 Toulouse, France.
authors: Fatima Bousejra-El
authors: FB
authors: Garah
authors: Jean-Luc
authors: JL
authors: Stigliani
authors: Frédéric
authors: F
authors: Coslédan
authors: Bernard
authors: B
authors: Meunier
authors: Anne
authors: A
authors: Robert
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D037621:Artemisinins / Q000737:chemistry / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011485:Protein Binding; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology
chemical_list: C513500:ATP6 protein, Plasmodium falciparum; D000962:Antimalarials; D037621:Artemisinins; C503606:DU1301; D004791:Enzyme Inhibitors; D011804:Quinolines; D012717:Sesquiterpenes; C031327:artemisinin; C037219:quinoline; D000252:Calcium-Transporting ATPases