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Instituto Oswaldo Cruz, Ministério da Saúde, Memórias do Instituto Oswaldo Cruz., 2(110), p. 255-258, 2015

DOI: 10.1590/0074-02760140415

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Structure-based drug design studies of the interactions ofent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparumsarco/endoplasmic reticulum Ca2+-ATPase PfATP6

Journal article published in 2015 by Oliveira,Alaí de Braga de, Varotti,Fernando de Pilla, Daniel Silqueira Martins Guimarães, Guimarães,Daniel Silqueira Martins, Comar Junior,Moacyr, Alaíde Braga de Oliveira, Taranto,Alex Gutterres, Alex Gutterres Taranto, Fernando de Pilla Varotti, Fonseca,Amanda Luisa Da, Ronan Batista, Batista,Ronan, Moacyr Comar Junior, Amanda Luisa da Fonseca ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Malaria is responsible for more deaths around the world than any other parasitic disease. Due to the emergence of strains that are resistant to the current chemotherapeutic antimalarial arsenal, the search for new antimalarial drugs remains urgent though hampered by a lack of knowledge regarding the molecular mechanisms of artemisi-nin resistance. Semisynthetic compounds derived from diterpenes from the medicinal plant Wedelia paludosa were tested in silico against the Plasmodium falciparum Ca 2+-ATPase, PfATP6. This protein was constructed by comparative modelling using the three-dimensional structure of a homologous protein, 1IWO, as a scaffold. Compound 21 showed the best docking scores, indicating a better interaction with PfATP6 than that of thapsigargin, the natural inhibitor. Inhibition of PfATP6 by diterpene compounds could promote a change in calcium homeostasis, leading to parasite death. These data suggest PfATP6 as a potential target for the antimalarial ent-kaurane diterpenes.