Inhibition of α-glucosidase and α-amylase by diaryl derivatives of imidazole-thione and 1,2,4-triazole-thiol.

The in vivo and in vitro effects of 4,5-diphenylimidazole-2-thione (1), 4,5-diphenyl-1,2,4-triazole-3-thiol (2) and 5-(2-hydroxyphenyl)-4-phenyl-1,2,4-triazole-3-thiol (3) on α-glucosidase and α-amylase were investigated. The in vivo inhibition has been found to be dose-dependent and to occur at a value less than LD50. The in vitro treatment of the enzymes by 4,5-diphenylimidazole-2-thione exhibited a reversible inhibition of the non-competitive type with Ki value of 3.5 and 6.5×10(-5) M for α-glucosidase and α-amylase, respectively. 4,5-diphenyl-1,2,4-triazole-3-thione showed a reversible inhibition of the competitive and non-competitive types, with Ki value of 10(-5) M magnitude, for α-glucosidase and α-amylase. On the other hand, 5-(o-hydroxyphenyl)-4-phenyl-1,2,4-triazole-3-thione did not display an inhibitory effect towards α-amylase but showed a potent inhibition of the competitive type for hepatic α-glucosidase with 10(-5) M magnitude of Ki value.