Abstract:
Benzo[b]thiophene has been implicated as molecular framework in the drug discovery against broad spectrum of
biological targets. In the antidiabetic drug regime, benzo[b]thiophene based SGLT2 and ALR2 inhibitors have
been recently developed but their potential towards α-amylase inhibition remained unexplored to date. In this
context, a series of novel small molecule benzo[b]thiophene-2-carboxylic acid derivatives (3a-p) was synthe-
sized, characterized, and evaluated for antidiabetic activity as α-amylase inhibitors. We found that, all benzo[b]
thiophene derivatives exhibited significant α-amylase inhibition with IC50 value ranging from 5.37 ± 0.25 μM to
29.89 ± 0.68 μM. The SAR studies showed benzo[b]thiophene carboxylate bearing bis(2-hydroxyethyl)amino
group (3b) was most potent with IC50 of 5.37 ± 0.25 μM compared to standard drug Acarbose (IC50 = 6.40 ±
0.14 μM). Further, the enzyme inhibition mechanism study regarded 3b as competitive inhibitor of α-amylase
with Ki value of 1.76 μM. A detailed in silico study was also performed in order to estimate binding properties,
drug likeness and predict toxicity profile of these agents. It was demonstrated that novel small molecule benzo[ thiophene derivative (3b) can effectively bind through H-bonding, hydrophobic and π-stacking interactions within α-amylase active site. Moreover, drug likeness and toxicity prediction studies suggested compound 3b as potential & safter α-amylase inhibitor. Overall, our present study disclosed a novel class of benzo[b]thiophene based α-amylase inhibitors and opened a template for further lead optimization and development
