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Docking and molecular dynamics studies of potential new leads against DBL3x derived from chondroitin sulfate A (CSA): a new approach for the treatment of malaria

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Autor(es):
Spadeto, Joao P. M. ; Cormanich, Rodrigo A. ; Franca, Tanos C. C. ; LaPlante, Steven R. ; Goncalves, Arlan S.
Número total de Autores: 5
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS; v. 40, n. 18, p. 10-pg., 2021-04-05.
Resumo

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 (AU)

Processo FAPESP: 18/03910-1 - Estudos físico-químicos de compostos orgânicos fluorados: abordagens experimental e teórica
Beneficiário:Rodrigo Antonio Cormanich
Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
Processo FAPESP: 20/06536-3 - Análise de substratos reativos da Fluorinase
Beneficiário:João Paulo Menezes Spadeto
Modalidade de apoio: Bolsas no Brasil - Mestrado