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2000
Volume 22, Issue 12
  • ISSN: 1570-1786
  • E-ISSN: 1875-6255

Abstract

The study aims to work on Computational Studies to Optimize Pyrazole Derivatives for Antibacterial Activity. A dataset of 28 Pyrazole derivatives having antibacterial activities was used to generate a pharmacophore hypothesis and a 3D-QSAR model. The established pharmacophore model (DHRRR_1) features three hydrogen bond donors (D), hydrophobic (H), and aromatic ring (R) features, exhibiting favorable parameters ( = 0.9031; Q2 = 0.9004). Hypothesis validation, enrichment analysis, and contour plot analysis were conducted, followed by virtual screening of the ChEMBL database using the optimized pharmacophore model and filtering based on the Lipinski rule of five. Docking was done with PDB ID 3G75 targeting DNA gyrase using Schrodinger software, further Desmond module of Schrodinger 2024-2 was used for MD simulations. The QSAR model was validated along with standard parameters. A library of NCE’s was designed with hypothesis DHRRR_1. Compounds that showed no violations in ADMET studies were further analysed for their interactions in the docking study. Eight compounds have shown zero violations in ADMET and have shown greater binding affinity in comparison to the standard Metronidazole. Further in the MD simulation results, instability of the complex 3G75-Comp D1 was analysed for 100 ns. This study provides a comprehensive approach for identifying novel Pyrazole-based antibacterial agents, highlighting compound D1 as a promising lead. Most promising compound D1 has indicated the role of the Hydroxy group, Pyrazole, and pyrrole ring for good antibacterial activity.

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2025-12-17

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Designing of Pyrazole Derivatives Using 3D-QSAR, ADMET, Molecular Docking and MD Simulations for Enhanced Antibacterial Properties
Lett. Org. Chem. 22, 946 (2025); https://doi.org/10.2174/0115701786360412250709155912
/content/journals/loc/10.2174/0115701786360412250709155912
/content/journals/loc/10.2174/0115701786360412250709155912
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  • Article Type:     Research Article
Keyword(s): DNA gyrase; hypothesis; Molecular docking; Nosocomial infections; QSAR; Virtual screening

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