Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca2+-ATPase PfATP6
| Autor: | Daniel Silqueira Martins Guimarães, Amanda Luisa da Fonseca, Ronan Batista, Moacyr Comar Junior, Alaíde Braga de Oliveira, Alex Gutterres Taranto, Fernando de Pilla Varotti |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Memorias do Instituto Oswaldo Cruz, Vol 110, Iss 2, Pp 255-258 (2015) |
| Druh dokumentu: | article |
| ISSN: | 1678-8060 0074-0276 |
| DOI: | 10.1590/0074-02760140415 |
| Popis: | 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 Ca2+-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. |
| Databáze: | Directory of Open Access Journals |
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