Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/17710
Title: Docking studies on the binding of quinoline derivatives and hematin to Plasmodium falciparum lactate dehydrogenase
Authors: Cortopassi, Wilian Augusto
Oliveira, Aline Alves
Guimarães, Ana Paula
Rennó, Magdalena Nascimento
Krettli, Antoniana Ursine
França, Tanos Celmar Costa
Affilliation: Instituto Militar de Engenharia. Laboratorio de Modelagem Molecular aplicada à Defesa Quimica e Biologica. Rio de Janeiro, RJ, Brasil/Pontificia Universidade Católica do Rio de Janeiro. Departamento de Quimica. Rio de Janeiro, RJ, Brasil
Instituto Militar de Engenharia. Laboratorio de Modelagem Molecular aplicada à Defesa Quimica e Biologica. Rio de Janeiro, RJ, Brasil
Instituto Militar de Engenharia. Laboratorio de Modelagem Molecular aplicada à Defesa Quimica e Biologica. Rio de Janeiro, RJ, Brasil
Universidade Federal do Rio de Janeiro. Curso de Farmacia. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Laboratorio de Malaria. Belo Horizonte, MG, Brasil
Instituto Militar de Engenharia. Laboratorio de Modelagem Molecular aplicada à Defesa Quimica e Biologica. Rio de Janeiro, RJ, Brasil
Abstract: The literature has reported that ferriprotoporphyrin IX (hematin) intoxicates the malarial parasite through competition with NADH for the active site of the enzyme lactate dehydrogenase (LDH). In order to avoid this, the parasite polymerizes hematin to hemozoin. The quinoline derivatives are believed to form complexes with dimeric hematin, avoiding the formation of hemozoin and still inhibiting LDH. In order to investigate this hypothesis we calculated the docking energies of NADH and some quinoline derivatives (in the free forms and in complex with dimeric hematin) in the active site of the Plasmodium falciparum LDH (PfLDH). Ours results showed better docking score values to the complexes when compared to the free compounds, pointing them as more efficient inhibitors of PfLDH. Further we performed Molecular Dynamics (MD) simulations studies on the best docking conformation of the complex chloroquine-dimeric hematin with PfLDH. Our in silico results corroborate experimental data suggesting a possible action route for the quinoline derivatives in the inhibition of PfLDH.
Keywords: Lactate dehydrogenase
PfLDH
Malaria
Plasmodium falciparum.
keywords: PfLDH
Malaria
Plasmodium falciparum.
Issue Date: 2011
Publisher: Taylor & Francis
Citation: CORTOPASSI, Wilian Augusto et al. Docking studies on the binding of quinoline derivatives and hematin to Plasmodium falciparum lactate dehydrogenase. Journal of Biomolecular Structure & Dynamics, v. 29, n. 1, p. 207-2018, 2011.
DOI: 10.1080/07391102.2011.10507383
ISSN: 1567-2026
Copyright: restricted access
Appears in Collections:MG - IRR - Artigos de Periódicos

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