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.
