A Structure-Based Design Strategy with Pyrazole-Pyridine Derivatives Targeting TNFα as Anti-Inflammatory Agents: E-Pharmacophore, Dynamic Simulation, Synthesis and In Vitro Evaluation.
| Autor: | Halder D; Epigenetic Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Shamirpet, Hyderabad, 500078, India.; Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India., Jeyaprakash RS; Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India., Ghosh B; Epigenetic Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Shamirpet, Hyderabad, 500078, India. |
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| Jazyk: | angličtina |
| Zdroj: | Chemistry & biodiversity [Chem Biodivers] 2024 Sep; Vol. 21 (9), pp. e202400778. Date of Electronic Publication: 2024 Aug 14. |
| DOI: | 10.1002/cbdv.202400778 |
| Abstrakt: | Any pathogenic attack, infection, or disease can initiate inflammation. It results in significant adverse consequences like inflammatory bowel disease, rheumatoid arthritis, etc. TNFα is one of the major pro-inflammatory cytokines for the progression of inflammation-the present study designed a series of hybrid compounds consisting of the pyrazole-pyridine moiety. Virtual screening was performed utilizing the e-pharmacophore hypothesis with the co-ligand of TNFα, screening, docking, and ADMET study. Induced fit docking, DFT analysis, and molecular dynamic simulation showed that the four best molecules - Dh1- Dh4-showed crucial interaction with Tyrosine, higher dock scores, and better stability than Diclofenac. Following the synthesis of hit molecules, an in vitro albumin denaturation IC (© 2024 Wiley-VHCA AG, Zurich, Switzerland.) |
| Databáze: | MEDLINE |
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