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
Mem. Inst. Oswaldo Cruz
; 110(2): 255-258, 04/2015. tab, graf
Article
em En
| LILACS
| ID: lil-744477
Biblioteca responsável:
BR1.1
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 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.
Palavras-chave
Texto completo:
1
Temas:
Saude_idoso
Base de dados:
LILACS
Assunto principal:
Sobreviventes
/
Neoplasias Gastrointestinais
/
Promoção da Saúde
Idioma:
En
Revista:
Mem. Inst. Oswaldo Cruz
Assunto da revista:
MEDICINA TROPICAL
/
PARASITOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Brasil