Integrative Approach for Designing Novel Triazole Derivatives as α-Glucosidase Inhibitors: QSAR, Molecular Docking, ADMET, and Molecular Dynamics Investigations

Oussama Abchir, Meriem Khedraoui, Hassan Nour, Imane Yamari, Abdelkbir Errougui, Abdelouahid Samadi, Samir Chtita

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

In response to the increasing prevalence of diabetes mellitus and the limitations associated with the current treatments, there is a growing need to develop novel medications for this disease. This study is focused on creating new compounds that exhibit a strong inhibition of alpha-glucosidase, which is a pivotal enzyme in diabetes control. A set of 33 triazole derivatives underwent an extensive QSAR analysis, aiming to identify the key factors influencing their inhibitory activity against α-glucosidase. Using the multiple linear regression (MLR) model, seven promising compounds were designed as potential drugs. Molecular docking and dynamics simulations were employed to shed light on the mode of interaction between the ligands and the target, and the stability of the obtained complexes. Furthermore, the pharmacokinetic properties of the designed compounds were assessed to predict their behavior in the human body. The binding free energy was also calculated using MMGBSA method and revealed favorable thermodynamic properties. The results highlighted three novel compounds with high biological activity, strong binding affinity to the target enzyme, and suitability for oral administration. These results offer interesting prospects for the development of effective and well-tolerated medications against diabetes mellitus. Dataset License: License under which the dataset is made available (CC0, CC-BY, CC-BY-SA, CC-BY-NC, etc.).

Original languageEnglish
Article number261
JournalPharmaceuticals
Volume17
Issue number2
DOIs
Publication statusPublished - Feb 2024

Keywords

  • ADMET
  • diabetes mellitus
  • dynamics simulation
  • molecular docking
  • QSAR
  • triazoles

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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