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.

• MeSH
• antigeny protozoální chemie   MeSH
• chondroitin sulfáty chemie   metabolismus   farmakologie   MeSH
• erytrocyty metabolismus   MeSH
• fosfáty MeSH
• glykosaminoglykany metabolismus   MeSH
• lidé MeSH
• malárie * komplikace   metabolismus   MeSH
• membránové proteiny metabolismus   MeSH
• parazitární komplikace těhotenství * metabolismus   MeSH
• placenta metabolismus   MeSH
• Plasmodium falciparum chemie   MeSH
• protozoální proteiny chemie   MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• sírany metabolismus   MeSH
• těhotenství MeSH
• tropická malárie * farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH