Identification of α-Mangostin as a Potential Inhibitor of Microtubule Affinity Regulating Kinase 4.
J Nat Prod
; 82(8): 2252-2261, 2019 08 23.
Article
em En
| MEDLINE
| ID: mdl-31343173
ABSTRACT
Microtubule affinity regulating kinase 4 (MARK4) is a potential drug target for neuronal disorders and several types of cancers. Filtration of naturally occurring compound libraries using high-throughput screening and enzyme assay suggest α-mangostin is a potential inhibitor of MARK4. Structure-based docking and 100 ns molecular dynamics simulation revealed that the binding of α-mangostin stabilizes the MARK4 structure. Enzyme inhibition and binding studies showed that α-mangostin inhibited MARK4 in the submicromolar range with IC50 = 1.47 µM and binding constant (Ka) 5.2 × 107 M-1. Cell-based studies suggested that α-mangostin inhibited the cell viability (MCF-7 and HepG2), induced apoptosis, arrested the cell cycle in the G0/G1 phase, and reduced tau-phosphorylation. This study implicates MARK4 as a new target of α-mangostin, adding an additional lead molecule to the anticancer repertoire.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Serina-Treonina Quinases
/
Xantonas
/
Inibidores de Proteínas Quinases
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2019
Tipo de documento:
Article