Design, synthesis and biological evaluation of vincamine derivatives as potential pancreatic ß-cells protective agents for the treatment of type 2 diabetes mellitus.
Eur J Med Chem
; 188: 111976, 2020 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-31918073
ABSTRACT
A series of vincamine derivatives were designed, synthesized and evaluated as pancreatic ß-cells protective agents for type 2 diabetes mellitus. Most of the compounds displayed potent pancreatic ß-cells protective activities and five derivatives were found to exhibit 20-50-fold higher activities than vincamine. Especially for compounds Vin-C01 and Vin-F03, exhibited a remarkable EC50 value of 0.22 µM and 0.27 µM, respectively. Their pancreatic ß-cells protective activities increased approximately 2 times than vincamine. In cell viability assay, compounds Vin-C01 and Vin-F03 could effectively promote ß-cell survival and protect ß-cells from STZ-induced apoptosis. Further cellular mechanism of action studies demonstrated that their potent ß-cells protective activities were achieved by regulating IRS2/PI3K/Akt signaling pathway. The present study evidently showed that compounds Vin-C01 and Vin-F03 were two more potent pancreatic ß-cells protective agents compared to vincamine and might serve as promising lead candidates for the treatment of type 2 diabetes mellitus.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Vincamina
/
Diseño de Fármacos
/
Sustancias Protectoras
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Diabetes Mellitus Tipo 2
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Células Secretoras de Insulina
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Hipoglucemiantes
Límite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Año:
2020
Tipo del documento:
Article