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
en En
| LILACS
| ID: lil-744477
Biblioteca responsable:
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
LILACS
Contexto en salud:
2_ODS3
/
3_ND
/
4_TD
Problema de salud:
2_enfermedades_transmissibles
/
2_muertes_prematuras_enfermedades_notrasmisibles
/
3_malaria
/
4_malaria
Asunto principal:
Sobrevivientes
/
Neoplasias Gastrointestinales
/
Promoción de la Salud
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Aged
/
Female
/
Humans
/
Male
País/Región como asunto:
Asia
Idioma:
En
Revista:
Mem. Inst. Oswaldo Cruz
Asunto de la revista:
MEDICINA TROPICAL
/
PARASITOLOGIA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Brasil