Title:Important Aspects of Post-Prandial Antidiabetic Drug, Acarbose
Volume: 16
Issue: 23
Author(s): Rajeev Kumar Singla, Radha Singh and Ashok Kumar Dubey
Affiliation:
Keywords:
α-Amylase inhibitor; GRIP docking; Antidiabetic agents; Acarbose; Pseudotetrasaccharide.
Abstract: Acarbose, a well known and efficacious α-amylase and α-glucosidase inhibitor, is a postprandial
acting antidiabetic drug. DNS-based α-amylase inhibitory assays showed that use of acarbose
at concentrations above 125 µg/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 α-amylase, but had weaker affinity for α -
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 α-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 α-amylase where the inhibitor (acarbose) bound more tightly, which possibly affected
the binding and hydrolysis of starch exerting its effective anti-diabetic function.
