Exploring antidiabetic potential of adamantyl-thiosemicarbazones via aldose reductase (ALR2) inhibition.
Bioorg Chem
; 92: 103244, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31541804
ABSTRACT
The role of aldose reductase (ALR2) in diabetes mellitus is well-established. Our interest in finding ALR2 inhibitors led us to explore the inhibitory potential of new thiosemicarbazones. In this study, we have synthesized adamantyl-thiosemicarbazones and screened them as aldehyde reductase (ALR1) and aldose reductase (ALR2) inhibitors. The compounds bearing phenyl 3a, 2-methylphenyl 3g and 2,6-dimethylphenyl 3m have been identified as most potent ALR2 inhibitors with IC50 values of 3.99⯱â¯0.38, 3.55⯱â¯0.26 and 1.37⯱â¯0.92⯵M, respectively, compared with sorbinil (IC50â¯=â¯3.14⯱â¯0.02⯵M). The compounds 3a, 3g, and 3m also inhibit ALR1 with IC50 value of 7.75⯱â¯0.28, 7.26⯱â¯0.39 and 7.04⯱â¯2.23⯵M, respectively. Molecular docking was also performed for putative binding of potent inhibitors with target enzyme ALR2. The most potent 2,6-dimethylphenyl bearing thiosemicarbazone 3m (IC50â¯=â¯1.37⯱â¯0.92⯵M for ALR2) and other two compound 3a and 3g could potentially lead for the development of new therapeutic agents.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiossemicarbazonas
/
Adamantano
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Aldeído Redutase
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Hipoglicemiantes
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article