Important Aspects of Post-Prandial Antidiabetic Drug, Acarbose

Acarbose, a well known and efficacious alpha-amylase and alpha-glucosidase inhibitor, is a postprandial acting antidiabetic drug. DNS-based alpha-amylase inhibitory assays showed that use of acarbose at concentrations above 125 mu g/ml resulted in release of reducing sugar in the reaction, an unexpected observation. Objective of the present study was to design experimental strategies to address this unusual finding. Acarbose was found to be susceptible to thermo-lysis. Further, besides being an inhibitor, it could also be hydrolyzed by porcine pancreatic alpha-amylase, but had weaker affinity for a amylase compared to starch. GRIP docking was done for the mechanistic analysis of the active site in the enzyme for substrate, inhibitor and, inhibitor's metabolite (K2). Interaction between acarbose and alpha-amylase involved significant hydrogen binding compared to that of starch, producing a stronger enzyme-inhibitor complex. Further, docking analysis led us to predict the site on alpha-amylase where the inhibitor (acarbose) bound more tightly, which possibly affected the binding and hydrolysis of starch exerting its effective anti-diabetic function.