In silico modeling of α-glucosidase, aldose reductase, and PPAR-γ with benzoyl/sulfonyl hydrazone derivatives using molecular docking, ADMET, and molecular dynamics simulations

Gizem Tatar Yılmaz; Bedriye Seda Kurşun Aktar; Emine Elçin Oruç-emre

In silico modeling of α-glucosidase, aldose reductase, and PPAR-γ with benzoyl/sulfonyl hydrazone derivatives using molecular docking, ADMET, and molecular dynamics simulations

Abstract

Type 2 diabetes mellitus (T2DM) is the most common type of diabetes and has become a serious public health problem in over the world. There are various antidiabetic drugs on the market, but most of these drugs cause many side effects such as diarrhea, kidney failure, musculoskeletal pain, and enlarged urinary system infections in the clinical treatment of T2DM. Therefore, there is a need for new antidiabetic drugs that can be used orally, are safe with improved efficacy, and reduced side effects. Today, drugs targeting alpha-glucosidase (α-glucosidase), peroxisome proliferator activating receptor gamma (PPAR-γ), and aldose reductase have an important role in the treatment of T2DM. This study is aimed to develop new antidiabetic agents with molecular modeling methods that are more effective, and specific and have fewer side effects than existing drug molecules for α-glucosidase, PPAR-γ, and aldose reductase. Herein, enzyme-ligand interaction mechanisms between target enzymes and 45 hydrazone compounds were examined by using molecular docking and molecular dynamics simulation methods. In addition, the ADME properties of these compounds and their pharmacokinetic suitability according to Lipinski and Veber’s rules were evaluated. Compound 2 has shown the best binding affinity against α-glucosidase, compound 27 for aldose reductase, and compound 4 for PPAR-γ and these compounds exhibited good ADME properties. Also, the best active hydrazone compounds have been observed to interact with key amino acid residues on target enzymes via hydrogen bonds. This information can guide the development of new antidiabetic agents by making important contributions to experimental studies.

Keywords

References

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Details

Primary Language

English

Subjects

Pharmacology and Pharmaceutical Sciences (Other)

Journal Section

Research Article

Authors

Gizem Tatar Yılmaz ^*
0000-0001-6642-6870
Türkiye

Bedriye Seda Kurşun Aktar
0000-0002-1492-3266
Türkiye

Emine Elçin Oruç-emre
0000-0001-6840-9660
Türkiye

Publication Date

June 28, 2025

Submission Date

December 25, 2022

Acceptance Date

March 17, 2023

Published in Issue

Year 2023 Volume: 27 Number: 4

IZ

https://izlik.org/JA39YD84CS

Cite

RIS / Bibtex

APA

Tatar Yılmaz, G., Kurşun Aktar, B. S., & Oruç-emre, E. E. (2025). In silico modeling of α-glucosidase, aldose reductase, and PPAR-γ with benzoyl/sulfonyl hydrazone derivatives using molecular docking, ADMET, and molecular dynamics simulations. Journal of Research in Pharmacy, 27(4), 1567-1576. https://izlik.org/JA39YD84CS

AMA

1.Tatar Yılmaz G, Kurşun Aktar BS, Oruç-emre EE. In silico modeling of α-glucosidase, aldose reductase, and PPAR-γ with benzoyl/sulfonyl hydrazone derivatives using molecular docking, ADMET, and molecular dynamics simulations. J. Res. Pharm. 2025;27(4):1567-1576. https://izlik.org/JA39YD84CS

Chicago

Tatar Yılmaz, Gizem, Bedriye Seda Kurşun Aktar, and Emine Elçin Oruç-emre. 2025. “In Silico Modeling of α-Glucosidase, Aldose Reductase, and PPAR-γ With Benzoyl Sulfonyl Hydrazone Derivatives Using Molecular Docking, ADMET, and Molecular Dynamics Simulations”. Journal of Research in Pharmacy 27 (4): 1567-76. https://izlik.org/JA39YD84CS.

EndNote

Tatar Yılmaz G, Kurşun Aktar BS, Oruç-emre EE (July 1, 2025) In silico modeling of α-glucosidase, aldose reductase, and PPAR-γ with benzoyl/sulfonyl hydrazone derivatives using molecular docking, ADMET, and molecular dynamics simulations. Journal of Research in Pharmacy 27 4 1567–1576.

IEEE

[1]G. Tatar Yılmaz, B. S. Kurşun Aktar, and E. E. Oruç-emre, “In silico modeling of α-glucosidase, aldose reductase, and PPAR-γ with benzoyl/sulfonyl hydrazone derivatives using molecular docking, ADMET, and molecular dynamics simulations”, J. Res. Pharm., vol. 27, no. 4, pp. 1567–1576, July 2025, [Online]. Available: https://izlik.org/JA39YD84CS

ISNAD

Tatar Yılmaz, Gizem - Kurşun Aktar, Bedriye Seda - Oruç-emre, Emine Elçin. “In Silico Modeling of α-Glucosidase, Aldose Reductase, and PPAR-γ With Benzoyl Sulfonyl Hydrazone Derivatives Using Molecular Docking, ADMET, and Molecular Dynamics Simulations”. Journal of Research in Pharmacy 27/4 (July 1, 2025): 1567-1576. https://izlik.org/JA39YD84CS.

JAMA

1.Tatar Yılmaz G, Kurşun Aktar BS, Oruç-emre EE. In silico modeling of α-glucosidase, aldose reductase, and PPAR-γ with benzoyl/sulfonyl hydrazone derivatives using molecular docking, ADMET, and molecular dynamics simulations. J. Res. Pharm. 2025;27:1567–1576.

MLA

Tatar Yılmaz, Gizem, et al. “In Silico Modeling of α-Glucosidase, Aldose Reductase, and PPAR-γ With Benzoyl Sulfonyl Hydrazone Derivatives Using Molecular Docking, ADMET, and Molecular Dynamics Simulations”. Journal of Research in Pharmacy, vol. 27, no. 4, July 2025, pp. 1567-76, https://izlik.org/JA39YD84CS.

Vancouver

1.Gizem Tatar Yılmaz, Bedriye Seda Kurşun Aktar, Emine Elçin Oruç-emre. In silico modeling of α-glucosidase, aldose reductase, and PPAR-γ with benzoyl/sulfonyl hydrazone derivatives using molecular docking, ADMET, and molecular dynamics simulations. J. Res. Pharm. [Internet]. 2025 Jul. 1;27(4):1567-76. Available from: https://izlik.org/JA39YD84CS