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

摘要

The alpha-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 alpha-amylase inhibition. It was found that most of the conjugates (14 a-j) exhibited significant alpha-amylase inhibition activity compared to the standard drug Acarbose. Off these, compound 14 b,14 c and 14 dwere most potent with IC50 value 0.13 mu M, 0.15 mu M and0.13 mu M 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) alpha-amylase enzyme. The results have shown fair corroboration between significant alpha-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 alpha-amylase for the treatment of Type 2 Diabetes mellitus.