In-Silico Design, Synthesis, and Pharmacological Evaluation of Oxadiazole-Based Selective Cyclo-oxygenase-2 Inhibitors
A series of oxadiazole-based five-membered heterocyclic derivatives was designed and synthesized with the intent of exclusive cyclo-oxygenase-2 (COX-2) inhibition to acquire anti-inflammatory activity without the presence of gastric toxicity. Oxadiazole-based novel analogs were designed by using bioisosteric substitutions and were screened against the macromolecular target by using docking-based virtual screening to identify their potential inhibitors. These selective COX-2 inhibitors were further evaluated for their stability within the binding cavity of macromolecular complex by performing molecular dynamic simulation for 100 ns. Selected compounds were synthesized by using Naphthalene-2-yl-acetic acid as a starting material based on the fundamental structure of naphthalene. The naphthalene ring and methylene bridge of naphthalene-2-yl-acetic acid were retained in the rational molecular design by replacing the carboxyl group with biologically significant groups like 1,3,4-oxadiazoles, with the goal of obtaining a novel, superior, and relatively safe anti-inflammatory molecule with better efficacy and optimized pharmacokinetics. Anti-inflammatory as well as analgesic properties of the compounds were evaluated experimentally for their pharmacological efficiency.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Assay and drug development technologies - 21(2023), 4 vom: 04. Mai, Seite 166-179 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kumar, Manish [VerfasserIn] |
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| Links: |
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| Themen: |
Acetic Acid |
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| Anmerkungen: |
Date Completed 19.06.2023 Date Revised 22.12.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1089/adt.2022.090 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM358204356 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a A series of oxadiazole-based five-membered heterocyclic derivatives was designed and synthesized with the intent of exclusive cyclo-oxygenase-2 (COX-2) inhibition to acquire anti-inflammatory activity without the presence of gastric toxicity. Oxadiazole-based novel analogs were designed by using bioisosteric substitutions and were screened against the macromolecular target by using docking-based virtual screening to identify their potential inhibitors. These selective COX-2 inhibitors were further evaluated for their stability within the binding cavity of macromolecular complex by performing molecular dynamic simulation for 100 ns. Selected compounds were synthesized by using Naphthalene-2-yl-acetic acid as a starting material based on the fundamental structure of naphthalene. The naphthalene ring and methylene bridge of naphthalene-2-yl-acetic acid were retained in the rational molecular design by replacing the carboxyl group with biologically significant groups like 1,3,4-oxadiazoles, with the goal of obtaining a novel, superior, and relatively safe anti-inflammatory molecule with better efficacy and optimized pharmacokinetics. Anti-inflammatory as well as analgesic properties of the compounds were evaluated experimentally for their pharmacological efficiency | ||
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| 650 | 4 | |a synthesis | |
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| 700 | 1 | |a Narang, Rakesh |e verfasserin |4 aut | |
| 700 | 1 | |a Devgun, Manish |e verfasserin |4 aut | |
| 700 | 1 | |a Khokra, Sukhbir Lal |e verfasserin |4 aut | |
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