Novel quinazolinone-based 2,4-thiazolidinedione-3-acetic acid derivatives as potent aldose reductase inhibitors.
Future Med Chem
; 9(18): 2147-2166, 2017 12.
Article
em En
| MEDLINE
| ID: mdl-29098865
ABSTRACT
AIM:
Targeting aldose reductase enzyme with 2,4-thiazolidinedione-3-acetic acid derivatives having a bulky hydrophobic 3-arylquinazolinone residue. MATERIALS &METHODS:
All the target compounds were structurally characterized by different spectroscopic methods and microanalysis, their aldose reductase inhibitory activities were evaluated, and binding modes were studied by molecular modeling.RESULTS:
All the synthesized compounds proved to inhibit the target enzyme potently, exhibiting IC50 values in the nanomolar/low nanomolar range. Compound 5i (IC50 = 2.56 nM), the most active of the whole series, turned out to be almost 70-fold more active than the only marketed aldose reductase inhibitor epalrestat.CONCLUSION:
This work represents a promising matrix for developing new potential therapeutic candidates for prevention of diabetic complications through targeting aldose reductase enzyme. [Formula see text].Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aldeído Redutase
/
Inibidores Enzimáticos
/
Quinazolinonas
/
Acetatos
Limite:
Humans
Idioma:
En
Revista:
Future Med Chem
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Egito