Computational investigation of the alkaloids of Pilocarpus microphyllus species as phytopharmaceuticals for the inhibition of sterol 14α-demethylase protease of Trypanosoma cruzi.
J Biomol Struct Dyn
; 41(6): 2555-2573, 2023 04.
Article
en En
| MEDLINE
| ID: mdl-35132947
ABSTRACT
Trypanosoma cruzi is a protozoan transmitted by the insect Triatoma infestans, popularly known as kissing bug. This protozoan causes the Chagas disease, a Neglected Tropical Disease. This study aimed to investigate, through DFT method and B3LYP hybrid functional, the physicochemical, pharmacokinetic, and pharmacodynamic properties of the alkaloids present in the leaves of the species Pilocarpus microphyllus (jaborandi) as a potential inhibitory activity on the protease sterol 14α-demethylase of T. cruzi associated with the techniques of molecular docking, molecular dynamics, MM-PBSA and ADMET predictions. The molecules of isopilosine, epiisopiloturine, epiisopilosine, and pilosine showed up the lowest binding energies by molecular docking, good human intestinal absorption, low penetration in the blood-brain barrier, antiprotozoal and anticarcinogenic activities in ADMET studies. It has been observed a better binding affinity of the sterol 14α-demethylase protease with isopilosine in molecular dynamics and MM-PBSA studies, which indicates it as a potential drug candidate for Chagas disease.Communicated by Ramaswamy H. Sarma.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trypanosoma cruzi
/
Enfermedad de Chagas
/
Pilocarpus
/
Alcaloides
Límite:
Humans
Idioma:
En
Revista:
J Biomol Struct Dyn
Año:
2023
Tipo del documento:
Article
País de afiliación:
Brasil