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Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca(2+)-ATPase PfATP6

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...

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Autores principales: Guimarães, Daniel Silqueira Martins, da Fonseca, Amanda Luisa, Batista, Ronan, Comar, Moacyr, de Oliveira, Alaíde Braga, Taranto, Alex Gutterres, Varotti, Fernando de Pilla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Instituto Oswaldo Cruz, Ministério da Saúde 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489458/
https://www.ncbi.nlm.nih.gov/pubmed/25946251
http://dx.doi.org/10.1590/0074-02760140415
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author Guimarães, Daniel Silqueira Martins
da Fonseca, Amanda Luisa
Batista, Ronan
Comar, Moacyr
de Oliveira, Alaíde Braga
Taranto, Alex Gutterres
Varotti, Fernando de Pilla
author_facet Guimarães, Daniel Silqueira Martins
da Fonseca, Amanda Luisa
Batista, Ronan
Comar, Moacyr
de Oliveira, Alaíde Braga
Taranto, Alex Gutterres
Varotti, Fernando de Pilla
author_sort Guimarães, Daniel Silqueira Martins
collection PubMed
description 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 artemisinin 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.
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spelling pubmed-44894582015-07-06 Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca(2+)-ATPase PfATP6 Guimarães, Daniel Silqueira Martins da Fonseca, Amanda Luisa Batista, Ronan Comar, Moacyr de Oliveira, Alaíde Braga Taranto, Alex Gutterres Varotti, Fernando de Pilla Mem Inst Oswaldo Cruz Short Communication 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 artemisinin 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. Instituto Oswaldo Cruz, Ministério da Saúde 2015-04 /pmc/articles/PMC4489458/ /pubmed/25946251 http://dx.doi.org/10.1590/0074-02760140415 Text en http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communication
Guimarães, Daniel Silqueira Martins
da Fonseca, Amanda Luisa
Batista, Ronan
Comar, Moacyr
de Oliveira, Alaíde Braga
Taranto, Alex Gutterres
Varotti, Fernando de Pilla
Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca(2+)-ATPase PfATP6
title Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca(2+)-ATPase PfATP6
title_full Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca(2+)-ATPase PfATP6
title_fullStr Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca(2+)-ATPase PfATP6
title_full_unstemmed Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca(2+)-ATPase PfATP6
title_short Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca(2+)-ATPase PfATP6
title_sort structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from wedelia paludosa with the plasmodium falciparum sarco/endoplasmic reticulum ca(2+)-atpase pfatp6
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489458/
https://www.ncbi.nlm.nih.gov/pubmed/25946251
http://dx.doi.org/10.1590/0074-02760140415
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