In this work the DBL3x domain of the erythrocyte membrane protein from Plasmodium Falciparum (PfEMP1), was revisited as a potential molecular target for the development of new drugs against malaria. This protein interacts with chondroitin sulfate A (CSA), a glycosaminoglycan present in the substance fundamental for connective tissues of vertebrates and is implicated in malaria complications in pregnant women. We performed molecular docking and molecular dynamic studies of DBL3x complexed with CSA and five analogues, where the sulfate group was replaced by phosphate, in order to evaluate if the better electrostatic interactions provided by phosphate groups could afford better binders capable of preventing the binding of CSA to DBL3x. Results suggest that all proposed compounds have high affinity towards DBL3x and could bind better to the DBL3x domain of PfEMP1 than CSA, qualifying as potential inhibitors of this protein and, therefore, new potential leads for the drug design against malaria.Communicated by Ramaswamy H. Sarma.

Department of Chemistry Faculty of Science University of Hradec Kralove Hradec Kralove Czech Republic

Federal Institute of Education Science and Technology of Espírito Santo Unit Vitória Espírito Santo Brazil

Federal Institute of Education Science and Technology of Espı́rito Santo Vila Velha Brazil

Federal University of Espírito Santo Unit Goiabeiras Vitoria Brazil

Institute of Chemistry University of Campinas Campinas Brazil

Laboratory of Molecular Modeling Applied to the Chemical and Biological Defense Military Institute of Engineering Rio de Janeiro Brazil

Université du Quebec INRS Centre Armand Frapier Santé Biotechnologie Laval Canada

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