Design, Synthesis and Antidiabetic Activity of Biphenylcarbonitrile-Thiazolidinedione Conjugates as Potential α-Amylase Inhibitors

Abstract

The á-amylase inhibition has been considered as an effective therapeutic approach against chronic Type 2 Diabetes mellitus (DM). In the present study, a series of biphenylcarbonitrilethiazolidinedione conjugates have been synthesized and evaluated for their antidiabetic activity via á-amylase inhibition. It was found that most of the conjugates (14a–j) exhibited significant á-amylase inhibition activity compared to the standard drug Acarbose. Off these, compound 14b, 14c and 14d were most potent with IC50 value 0.13 ìM, 0.15 ìM and 0.13 ìM respectively. To ascertain ligand-receptor interactions, the in silico molecular docking studies of these conjugates (14a–j) have been carried out into the Acarbose active site of barley (malt) á-amylase enzyme. The results have shown fair corroboration between significant á-amylase inhibition activity of 14b, 14c and 14d and their docking scores compared to the standard drug Acarbose. This study demonstrated that biphenylcarbonitrile-thiazolidinedione conjugate could be a plausible pharmacophore for targeting á-amylase for the treatment of Type 2 Diabetes mellitus.