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

The α‐amylase inhibition has been considered as an effective therapeutic approach against chronic Type 2 Diabetes mellitus (DM). In the present study, a series of biphenylcarbonitrile‐thiazolidinedione conjugates have been synthesized and evaluated for their antidiabetic activity via α‐amylase inhibition. It was found that most of the conjugates ( 14 a – j ) exhibited significant α‐amylase inhibition activity compared to the standard drug Acarbose. Off these, compound 14 b , 14 c and 14 d were most potent with IC 50 value 0.13 μM, 0.15 μM and 0.13 μM respectively. To ascertain ligand‐receptor interactions, the in silico molecular docking studies of these conjugates ( 14 a – j ) have been carried out into the Acarbose active site of barley (malt) α‐amylase enzyme. The results have shown fair corroboration between significant α‐amylase inhibition activity of 14 b , 14 c and 14 d and their docking scores compared to the standard drug Acarbose. This study demonstrated that biphenylcarbonitrile‐thiazolidinedione conjugate could be a plausible pharmacophore for targeting α‐amylase for the treatment of Type 2 Diabetes mellitus.