Docking Studies of Structurally Diverse Antimalarial Drugs Targeting PfATP6: No Correlation between in silico Binding Affinity and in vitro Antimalarial Activity.
Identifieur interne : 001876 ( Main/Exploration ); précédent : 001875; suivant : 001877Docking Studies of Structurally Diverse Antimalarial Drugs Targeting PfATP6: No Correlation between in silico Binding Affinity and in vitro Antimalarial Activity.
Auteurs : Fatima Bousejra-El Garah ; Jean-Luc Stigliani ; Frédéric Coslédan [France] ; Bernard Meunier [France] ; Anne Robert [France]Source :
- ChemMedChem [ 1860-7179 ] ; 2009-09-04.
English descriptors
- Teeft :
- Acridine, Acridine moiety, Affinity, Agents chemother, Amine, Amino acids, Antimalarial, Antimalarial activity, Antimalarial agents, Antimalarial drug, Antimalarial drugs, Antimalarial drugs figure, Antimicrob, Artemisinin, Artemisinin derivatives, Artemisone, Atpase, Autodock4, Binding affinities, Binding affinity, Binding energies, Binding energy, Binding site, Biol, Chem, Chemmedchem, Chemother, Chloroquine, Conformation, Crystal structure, Deoxyartemisinin, Derivative, Docking, Docking protocol, Docking studies, Ebind, Ebind kcal, Falciparum, Falciparum strain, Free base, Gmbh, Heme, Heme alkylation, Hydrophobic, Hydrophobic interactions, Inhibition constants, Kcal, Kgaa, Ligand, Methyl group, Meunier, Moiety, Octyl chain, Parasite, Parasite growth, Peroxide, Peroxide bond, Pfatp6, Pfatp6 model, Protonated, Quinoline, Quinoline moiety, Same location, Serca1a, Thapsigargin, Trioxane, Trioxaquines, Verlag, Verlag gmbh, Weinheim, Weinheim chemmedchem, Xenopus oocytes.
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.
Docking studies of antimalarial drugs: A homology model of PfATP6, a Plasmodium falciparum calcium ATPase was constructed using the crystal structure of the mammalian homologue SERCA1a. Antimalarial agents containing peroxide were then docked with both the PfATP6 model and the SERCA1a X‐ray structure. Their predicted binding affinities do not correlate with their antimalarial activities.
Url:
DOI: 10.1002/cmdc.200900200
Affiliations:
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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.</div><div type="abstract" xml:lang="en">Docking studies of antimalarial drugs: A homology model of PfATP6, a Plasmodium falciparum calcium ATPase was constructed using the crystal structure of the mammalian homologue SERCA1a. Antimalarial agents containing peroxide were then docked with both the PfATP6 model and the SERCA1a X‐ray structure. 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