Dihydropyrano [2,3-c] pyrazole: Novel in vitro inhibitors of yeast alpha-glucosidase

作者：Kashtoh Hamdy; Muhammad Munira Taj; Khan Jalaluddin J A; Rasheed Saima; Khan Ajmal; Perveen Shahnaz; Javaid Kulsoom; Atia tul Wahab; Khan Khalid Mohammed^*; Choudhary M Iqbal^*

来源：Bioorganic Chemistry, 2016, 65: 61-72.

DOI：10.1016/j.bioorg.2016.01.008

• Dihydropyrano [2,3-c] pyrazole
• alpha-Glucosidase inhibition
• Post-prandial hyperglycemia
• Diabetes

Inhibition of alpha-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 a-glucosidase inhibitory activity. Compounds 1, 4, 22, 30, and 33 were found to be the potent inhibitors of the yeast alpha-glucosidase enzyme. Mechanistic studies on most potent compounds reveled that 1, 4, and 30 were non-competitive inhibitors (K-i = 9.75 +/- 0.07, 46 +/- 0.0001, and 69.16 +/- 0.01 mu M, respectively), compound 22 is a competitive inhibitor (K-i = 190 +/- 0.016 mu M), while 33 was an uncompetitive inhibitor (K-i = 45 +/- 0.0014 mu M) 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 alpha-glucosidase enzyme for further investigation as anti-diabetic agents.

• 出版日期2016-4