Exploring the in vitro anti-diabetic potential and in silico studies of 2, 3 and 2, 6-dichloroIndolinone

Abdur Rauf; Waqas Alam; Momin Khan; Hany W. Darwish; Maria Daglia; Ahmed A. Elhenawy; Haroon Khan

doi:10.33393/dti.2025.3271

Authors

Abdur Rauf Department of Pharmacy, Abdul Wali Khan University, Mardan - Pakistan https://orcid.org/0009-0009-4680-4956
Waqas Alam Department of Pharmacy, Abdul Wali Khan University, Mardan - Pakistan https://orcid.org/0000-0001-8329-9180
Momin Khan Department of Chemistry, Abdul Wali Khan University, Mardan - Pakistan
Hany W. Darwish Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh - Kingdom of Saudi Arabia
Maria Daglia Department of Pharmacy, University of Naples Federico II- Italy https://orcid.org/0000-0002-4870-7713
Ahmed A. Elhenawy Department of Chemistry, Faculty of Science, Al-Azhar University, Cairo - Egypt https://orcid.org/0000-0003-2893-0376
Haroon Khan Department of Pharmacy, Abdul Wali Khan University, Mardan - Pakistan and Department of Pharmacy, Korea University, Sejong - South Korea https://orcid.org/0000-0002-1736-4404

DOI:

https://doi.org/10.33393/dti.2025.3271

Keywords:

2, 3 and 2, 6-dichloroIndolinone, α-glucosidase/α-amylase inhibition, Molecular docking, Molecular simulation

Abstract

Introduction: Adequate hyperglycemic control is still a huge challenge with the clinically used therapeutics. New, more effective anti-diabetic agents are on the top list of drug discovery projects.

Methods: This article deals with the in vitro anti-diabetic potential of 2, 3 dichloroIndolinone (C1) and 2, 6-dichloroIndolinone (C2) on α-glucosidase and α-amylase followed by in silico analysis.

Results: Both compounds, C-1 and C-2, caused significant inhibition of α-glucosidase at various test concentrations with IC₅₀ of 35.266 μM and 38. 379 μM, respectively. Similarly, compounds C-1 and C-2 elicited significant anti-α-amylase action with IC₅₀ values of 42.449 μM and 46.708 μM, respectively. The molecular docking investigation regarding the α-glucosidase and α-amylase binding site was implemented to attain better comprehension with respect to the pattern in which binding mechanics occur between the C1 and C2 molecules and the active sites, which illustrated a higher binding efficacy in appraisal with reference inhibitor and acarbose. The interactions between the active compounds C1 and C2 with the active site residues were mainly polar bonds, hydrogen bonding, π−π, and π−H interactions, which contributed to a strong alignment with the enzyme backbone. Similarly, effective binding is frequently indicated by a strong and stable hydrogen-bonding pattern, which is suggested by the minimal fluctuation in MM-PBSA values.

Conclusion: In short, this study will contribute to providing these compounds with an improved anti-diabetic profile and decreased toxicity.

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