From Myricetin to the Discovery of Novel Natural Human ENPP1 Inhibitors: A Virtual Screening, Molecular Docking, Molecular Dynamics Simulation, and MM/GBSA Study.
Molecules
; 27(19)2022 Sep 21.
Article
en En
| MEDLINE
| ID: mdl-36234712
ABSTRACT
It was recently revealed that naturally occurring myricetin can inhibit ectonucleotidase ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which, in turn, can treat ischemic cardiac injury. However, due to myricetin's poor druggability, its further developments are relatively limited, which necessitates the discovery of novel ENPP1-inhibiting myricetin analogs as alternatives. In this study, the binding model of myricetin with ENPP1 was elucidated by molecular docking and molecular dynamics studies. Subsequently, virtual screening on the self-developed flavonoid natural product database (FNPD), led to the identification of two flavonoid glycosides (Cas No 1397173-50-0 and 1169835-58-8), as potential ENPP1 inhibitors. Docking scores and MM/GBSA binding energies predicted that they might have higher inhibitory effects than myricetin. This study provides a strong foundation for the future development of ischemic cardiac injury drugs.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Productos Biológicos
/
Simulación de Dinámica Molecular
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
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Screening_studies
Límite:
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article