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

Author(s)

Spadeto, Joao P. M. ; Cormanich, Rodrigo A. ; Franca, Tanos C. C. ; LaPlante, Steven R. ; Goncalves, Arlan S.

• Document type: Journal article
• Source: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS; v. 40, n. 18, p. 10-pg., 2021-04-05.

Abstract

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)

• FAPESP's process: 18/03910-1 - Physicochemical studies of fluorinated organic compounds: experimental and theoretical approaches
• Grantee: Rodrigo Antonio Cormanich
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/06536-3 - Fluorinase reactive substrate analysis
• Grantee: João Paulo Menezes Spadeto
• Support Opportunities: Scholarships in Brazil - Master