Title: | Synthesis, antidiabetic aSynthesis, antidiabetic activity and in silico studies of benzo[b]thiophene based small molecule α-amylase inhibitors |
Authors: | Joshi, Rupal J. Dholariya, PMonil Savankumar, R Chothani, a |
Keywords: | Benzo[b]thiophene α-Amylase inhibitor Antidiabetic Molecular docking In silico |
Issue Date: | 2024 |
Publisher: | Journal of Molecular Structure |
Citation: | Joshi, R. J., Dholariya, M. P., Chothani, S. R., Chamakiya, C. A., Varu, H. L., Karmur, M. B., ... & Kapuriya, N. P. (2024). Synthesis, antidiabetic activity and in silico studies of benzo [b] thiophene based small molecule α-amylase inhibitors. Journal of Molecular Structure, 1312, 138570. |
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 |
URI: | http://10.9.150.37:8080/dspace//handle/atmiyauni/1573 |
Appears in Collections: | 01. Journal Articles |
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Synthesis, antidiabetic activity and in silico studies of benzo[b]thiophene.pdf | 3.53 MB | Adobe PDF | View/Open |
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