In Silico Approach for Developing New Anti-Tuberculosis Drug Candidates: 3D-QSAR, Molecular Docking and ADME Studies of Pretomanid Derivatives

Document Type : Regular Article

Authors

1 Chemistry Department, Faculty of sciences, Blida 1 University, B.P 270 Route de Soumaa, Blida, 09000, Algeria

2 Chemical Engineering Department, Faculty of Chemical Engineering, University of Salah Boubnider Constantine 3, Algeria

3 Natural Substances and Molecular Chemistry laboratory (SOOM), Faculty of Science, Moulay Ismail University of Meknes, Morocco

10.22036/pcr.2024.425052.2448

Abstract

Tuberculosis (TB) is one of the top ten causes of mortality worldwide, necessitating the discovery of new molecules with potential anti-tuberculosis activity. In this study, Pretomanid derivatives as potent anti-TB agents were collected from the literature to generate a 3D-QSAR model and conduct molecular docking. The 3D-QSAR model was successfully generated with a high regression coefficient R²= 0.98 and an excellent cross-validated determination coefficient Q2cv= 0.51 for the training set. Furthermore, the model developed showed good predictive ability, with a high predictive value Q2= 0.75 for the test set. The generated 3D contour cubes were applied to find the structural properties necessary to inhibit Deazaflavin-dependent nitroreductase. Then, the results were used to discover novel molecules with a potential anti-tuberculosis activity using the structure-based virtual screening. Based on successful results obtained by virtual screening, twelve compounds were selected as potential inhibitors of the Ddn with highly predicted activities, binding interactions, and acceptable ADME properties.

Graphical Abstract

In Silico Approach for Developing New Anti-Tuberculosis Drug Candidates: 3D-QSAR, Molecular Docking and ADME Studies of Pretomanid Derivatives

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Main Subjects

Physical Chemistry Research
Volume 12, Issue 3 - Serial Number 43
September 2024
Pages 729-743

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History

  • Receive Date: 15 November 2023
  • Revise Date: 25 January 2024
  • Accept Date: 29 January 2024

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