Dihydropyrano [2,3-c] pyrazole: Novel in vitro inhibitors of yeast α-glucosidase.
Bioorg Chem
; 65: 61-72, 2016 Apr.
Article
in En
| MEDLINE
| ID: mdl-26874344
ABSTRACT
Inhibition of α-glucosidase enzyme activity is a reliable approach towards controlling post-prandial hyperglycemia associated risk factors. During the current study, a series of dihydropyrano[2,3-c] pyrazoles (1-35) were synthesized and evaluated for their α-glucosidase inhibitory activity. Compounds 1, 4, 22, 30, and 33 were found to be the potent inhibitors of the yeast α-glucosidase enzyme. Mechanistic studies on most potent compounds reveled that 1, 4, and 30 were non-competitive inhibitors (Ki=9.75±0.07, 46±0.0001, and 69.16±0.01µM, respectively), compound 22 is a competitive inhibitor (Ki=190±0.016µM), while 33 was an uncompetitive inhibitor (Ki=45±0.0014µM) of the enzyme. Finally, the cytotoxicity of potent compounds (i.e. compounds 1, 4, 22, 30, and 33) was also evaluated against mouse fibroblast 3T3 cell line assay, and no toxicity was observed. This study identifies non-cytotoxic novel inhibitors of α-glucosidase enzyme for further investigation as anti-diabetic agents.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrans
/
Pyrazoles
/
Saccharomyces cerevisiae
/
Alpha-Glucosidases
/
Glycoside Hydrolase Inhibitors
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Bioorg Chem
Year:
2016
Document type:
Article
Affiliation country: