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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Instituto Oswaldo Cruz, Ministério da Saúde
2015
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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. |
format | Online Article Text |
id | pubmed-4489458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Instituto Oswaldo Cruz, Ministério da Saúde |
record_format | MEDLINE/PubMed |
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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