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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Development of Potential Antidiabetic Agents using 2D and 3D QSAR, Molecular Docking and ADME Properties In-silico Studies of α-amylase Inhibitors

Author(s): Kalusing S. Padvi, Aniket P. Sarkate*, Shashikant V. Bhandari and Mahadevi V. Kendre

Volume 21, Issue 16, 2024

Published on: 21 February, 2024

Page: [3443 - 3464] Pages: 22

DOI: 10.2174/0115701808279839240206123454

Price: $65

Abstract

Background: A series of 2-arylbenzimidazole derivatives were designed and developed as antidiabetic drugs using 2D and 3D QSAR, molecular docking and ADME studies.

Methods: All molecular modeling studies were performed using Molecular Design Suite V-Life MDS software. New chemical entities (NCEs) were designed based on the results of 2D and 3D QSAR studies. Docking studies were performed with the designed NCEs in PDB: 5E0F and the results were compared with the receptor ligand. According to the ADME results, all the proposed compounds have good oral absorption, correct molecular weight, QPlogPo/w. All units show oral absorption above 80%, it is considered well absorbed. All the proposed units show satisfactory results in the area. This indicated that these NCEs have little or no chance of failure in the final stages of the drug development process.

Results: The 2D QSAR results showed that the descriptor k2alpha, T_T_N_5, IodinesCount and BrominesCount play the most important role in determining the inhibitory activity of α-amylase. Although 3D QSAR showed that, the q2 and Pred_r2 values of the model (SA kNN MFA model) were 0.7476 and 0.6932. The G score of the proposed compound numbers mol-1, mol-2, mol-3, mol- 4, mol-5, mol-6, mol-7 and mol-8 are better compared to the standards, indicating that the proposed compounds have good binding properties affinity to bind to α-amylase.

Conclusion: These investigations have produced statistically significant and exceptionally reliable 2D and 3D Quantitative Structure-Activity Relationship (QSAR) models for antidiabetic medications, particularly α-amylase inhibitors. Furthermore, docking experiments involving the α-amylase enzyme have revealed that the binding energies of most Novel Chemical Entities (NCEs) are comparable to those of the established standards. Docking studies with α-amylase enzyme showed that most NCEs have binding energies comparable to the standard.

Keywords: Antidiabetic, QSAR, NCE's, α-Amylase, docking, ADME.

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