Novel phthalimido-benzenesulfonamide hybrid as a potent α-glucosidase inhibitor: Synthesis, biological evaluation, molecular docking and in silico ADME prediction

Şirin Uysal Ol; Zeynep Soyer

doi:10.55971/EJLS.1772928

Novel phthalimido-benzenesulfonamide hybrid as a potent α-glucosidase inhibitor: Synthesis, biological evaluation, molecular docking and in silico ADME prediction

Abstract

Diabetes mellitus is a global health crisis, recognized as one of the 21st century’s most significant challenges. Therapeutic strategies for managing Type 2 Diabetes mellitus (T2DM) frequently involve α-glucosidase inhibitors (AGIs), which mitigate postprandial glucose excursions by delaying carbohydrate digestion. This study focuses on the synthesis, characterization, and in vitro α-glucosidase inhibitory evaluation of a novel phthalimido-benzenesulfonamide hybrid compound, specifically 4-phthalimido-N-(5-chloro-2-pyridylamino)benzenesulfonamide. Additionally, enzyme kinetics and molecular docking studies were performed on this compound to reveal enzyme inhibition models and ligand-enzyme binding interactions. Furthermore, we used the PreADMET web service to calculate the ADME/Tox properties of the compound. According to the biological activity data, the target compound exhibited α-glucosidase inhibition (IC50 = 1240.52 ± 316.98 µM) comparable to the reference drug acarbose (IC50 = 1210.96 ± 0.17 μM), positioning it as a promising scaffold for future antidiabetic drug development efforts. Molecular docking studies provided informative clues for the ligand-enzyme binding interactions to estimate allosteric cavities (A1-A5) of the homology model of α-glucosidase. Kinetic analysis revealed an uncompetitive inhibition, with reduced Kₘ and Vₘₐₓ, confirming an allosteric mechanism. In silico ADME/Tox predictions suggested that the compound had favorable ADME/Tox properties. Overall, this hybrid compound represents a promising lead for next-generation AGIs with reduced side effects.

Keywords

Supporting Institution

This research received no grant from any funding agency/sector.

Ethical Statement

Not applicable, because this article does not contain any studies with human or animal subjects.

Thanks

The authors gratefully acknowledge Dr. Güneş Çoban and MSc. Merve ARI for performing molecular docking and enzyme kinetic studies, respectively. Authors also thank to the Pharmaceutical Sciences Research Centre (FABAL) at Ege University, Faculty of Pharmacy for spectral analyses of the compounds.

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Details

Primary Language

English

Subjects

Molecular Docking, Pharmaceutical Chemistry, Computational Chemistry

Journal Section

Research Article

Authors

Şirin Uysal Ol
0000-0003-0741-3652
Türkiye

Zeynep Soyer ^*
0000-0002-7426-0345
Türkiye

Early Pub Date

November 25, 2025

Publication Date

December 31, 2025

Submission Date

August 27, 2025

Acceptance Date

September 25, 2025

Published in Issue

Year 2025 Volume: 4 Number: 3

DOI

https://doi.org/10.55971/EJLS.1772928

IZ

https://izlik.org/JA44ZK66PD

Cite

RIS / Bibtex

APA

Uysal Ol, Ş., & Soyer, Z. (2025). Novel phthalimido-benzenesulfonamide hybrid as a potent α-glucosidase inhibitor: Synthesis, biological evaluation, molecular docking and in silico ADME prediction. European Journal of Life Sciences, 4(3), 145-154. https://doi.org/10.55971/EJLS.1772928

AMA

1.Uysal Ol Ş, Soyer Z. Novel phthalimido-benzenesulfonamide hybrid as a potent α-glucosidase inhibitor: Synthesis, biological evaluation, molecular docking and in silico ADME prediction. Eur J Life Sci. 2025;4(3):145-154. doi:10.55971/EJLS.1772928

Chicago

Uysal Ol, Şirin, and Zeynep Soyer. 2025. “Novel Phthalimido-Benzenesulfonamide Hybrid As a Potent α-Glucosidase Inhibitor: Synthesis, Biological Evaluation, Molecular Docking and in Silico ADME Prediction”. European Journal of Life Sciences 4 (3): 145-54. https://doi.org/10.55971/EJLS.1772928.

EndNote

Uysal Ol Ş, Soyer Z (December 1, 2025) Novel phthalimido-benzenesulfonamide hybrid as a potent α-glucosidase inhibitor: Synthesis, biological evaluation, molecular docking and in silico ADME prediction. European Journal of Life Sciences 4 3 145–154.

IEEE

[1]Ş. Uysal Ol and Z. Soyer, “Novel phthalimido-benzenesulfonamide hybrid as a potent α-glucosidase inhibitor: Synthesis, biological evaluation, molecular docking and in silico ADME prediction”, Eur J Life Sci, vol. 4, no. 3, pp. 145–154, Dec. 2025, doi: 10.55971/EJLS.1772928.

ISNAD

Uysal Ol, Şirin - Soyer, Zeynep. “Novel Phthalimido-Benzenesulfonamide Hybrid As a Potent α-Glucosidase Inhibitor: Synthesis, Biological Evaluation, Molecular Docking and in Silico ADME Prediction”. European Journal of Life Sciences 4/3 (December 1, 2025): 145-154. https://doi.org/10.55971/EJLS.1772928.

JAMA

1.Uysal Ol Ş, Soyer Z. Novel phthalimido-benzenesulfonamide hybrid as a potent α-glucosidase inhibitor: Synthesis, biological evaluation, molecular docking and in silico ADME prediction. Eur J Life Sci. 2025;4:145–154.

MLA

Uysal Ol, Şirin, and Zeynep Soyer. “Novel Phthalimido-Benzenesulfonamide Hybrid As a Potent α-Glucosidase Inhibitor: Synthesis, Biological Evaluation, Molecular Docking and in Silico ADME Prediction”. European Journal of Life Sciences, vol. 4, no. 3, Dec. 2025, pp. 145-54, doi:10.55971/EJLS.1772928.

Vancouver

1.Şirin Uysal Ol, Zeynep Soyer. Novel phthalimido-benzenesulfonamide hybrid as a potent α-glucosidase inhibitor: Synthesis, biological evaluation, molecular docking and in silico ADME prediction. Eur J Life Sci. 2025 Dec. 1;4(3):145-54. doi:10.55971/EJLS.1772928