In vitro, in silico and Pharmaco-toxicological Efficiencies of some Triazole Derivatives on Inhibition of Digestive Enzyme Alpha-amylase

Abstract

Obesity is one of the main health problems associated with a range of diseases. Genetic disposition is related to the risk for obesity but external conditions such lifestyle also increase the incidence. Current COVID-19 pandemic conditions around the globe have been reported to increase the cases of Type-2 diabetes mellitus (T2DM) due to prolonged sedentary life. Among the various treatment modalities, applications of α-amylase inhibitors are commonly used worldwide. Commercially available anti-diabetic drugs are potent inhibitors of α-amylase that reduce postprandial hyperglycemia. In this study, α-amylase inhibition efficiencies of some 1,2,4-triazole derivatives were evaluated. Furthermore, it has been attempted to determine the possible inhibition mechanism of the strongest inhibitor compound among the 8 candidate molecules for α-amylase. Compound VII showed the strongest inhibition on α-amylase activity with low IC50 value (150 µM). An inhibitory kinetic analysis on α-amylase activity by Compound VII was found to be reversible and uncompetitive. Furthermore, molecular docking studies with this molecule showed that it could bind to the catalytic site of the enzyme by performing weak interactions with Ser56, Tyr59, Tyr62, Asp176, Asp274 and Leu142 residues. Cytotoxic potential of Compound VII on amylase overexpressing AR42J HIGHLIGHTS• T2DM is increasing rapidly in the world and this brings a constant search for drugs.• Compound VII showed the strongest inhibition on α-amylase activity with low IC50 value.• Compound VII, amylase inhibition activity was found to be strong on AR42J cells.• Compound VII may play role an alternative and non-cytotoxic α-amylase inhibitor for T2DM.