Pyrazole and pyrazolone derivatives as specific α-glucosidase inhibitors: in vitro combined with in silico, hemolytic and cytotoxicity studies

Abstract

Pyrazole and pyrazolone derivatives have the potential to be promising anti-diabetic drugs. In this work, we evaluate the inhibitory effect on α-amylase and α-glucosidase of pyrazole and pyrazolones via in vitro study using acarbose as a positive control. The results showed that 5-methyl-4-[(4-methylphenyl)sulfanyl]-1,2- dihydro-3H-pyrazol-3-one (Compound 3), 3,5,5-trimethyl-1-[(4-methylphenyl)sulfonyl]- 4,5-dihydro-1H-pyrazole (Compound 4) and acarbose inhibit α-amylase with IC50 of 1.95 ± 0.098 mg/mL, 0.08 ± 0.004 mg/mL, and 0.15 ± 0.008 mg/mL (p < 0.05), respectively. The 3,4-dimethylpyrano [2,3-c]pyrazol-6(2H)-one (Compound 1) has no inhibitory effect of α-amylase. The compounds 3 and 4 inhibit α-glucosidase with an IC50 value of 1.55 ± 0.078 mg/mL and 0.36 ± 0.018 mg/mL (p < 0.05), respectively while compound 1 and acarbose have a comparable inhibition against α-glucosidase with an IC50 value of 0.1 ± 0.005 mg/mL, and 0.125 ± 0.006 mg/mL (p < 0.05), respectively. The in silico study confirmed the specificity of this compound with a difference in the binding energy and number of bonds in the case of α-glucosidase. In addition, the cytotoxicity and the hemolytic studies confirmed the potential of compound 1 as a safe and specific anti-postprandial hyperglycemia drug.