Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants
In the present study, we used benzimidazolone as a starting material to efficiently synthesize several hybrid compounds of pyrazole benzimidazolone derivatives by the 1,3-dipolar cycloaddition reaction. These compounds were obtained in average yields and were characterized by NMR (<sup>1</s...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/12/1648 |
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| author | Mohamed Adardour Marouane Ait Lahcen Mehdi Oubahmane Walid Ettahiri Ismail Hdoufane Hafida Bouamama Mohammed M. Alanazi Driss Cherqaoui Mustapha Taleb Elena Zaballos Garcia Abdesselam Baouid |
| author_facet | Mohamed Adardour Marouane Ait Lahcen Mehdi Oubahmane Walid Ettahiri Ismail Hdoufane Hafida Bouamama Mohammed M. Alanazi Driss Cherqaoui Mustapha Taleb Elena Zaballos Garcia Abdesselam Baouid |
| author_sort | Mohamed Adardour |
| collection | DOAJ |
| description | In the present study, we used benzimidazolone as a starting material to efficiently synthesize several hybrid compounds of pyrazole benzimidazolone derivatives by the 1,3-dipolar cycloaddition reaction. These compounds were obtained in average yields and were characterized by NMR (<sup>1</sup>H and <sup>13</sup>C) and HRMS analysis. The antioxidant activity of the synthesized compounds <b>5</b>(<b>a</b>–<b>c</b>) and <b>6</b>(<b>a</b>–<b>c</b>) was evaluated using in vitro reduction assays, including ferric reducing antioxidant power (FRAP) and total antioxidant capacity (TAC). The results indicated that products <b>5c</b>, <b>6b</b>, and <b>6c</b> exhibit higher antioxidant activity compared to the reference compounds and showed a remarkable ability to effectively remove the radical at IC<sub>50</sub> (14.00 ± 0.14, 12.47± 0.02, and 12.82 ± 0.10 µM, respectively) under the TAC assessment. Conversely, compound <b>6c</b> showed excellent activity at IC<sub>50</sub> (68.97 ± 0.26 µM) in the FRAP assay. We carried out molecular docking and dynamics simulations to investigate the binding mode and stability of <b>5c</b>, <b>6b</b>, and <b>6c</b> in the active site of human Peroxiredoxin 5. An ADMET study was conducted to determine the drug properties of the synthesized compounds. |
| first_indexed | 2024-03-08T20:26:59Z |
| format | Article |
| id | doaj.art-6b6b3773cfa7401c98cdc26cb0259d90 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-08T20:26:59Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-6b6b3773cfa7401c98cdc26cb0259d902023-12-22T14:31:18ZengMDPI AGPharmaceuticals1424-82472023-11-011612164810.3390/ph16121648Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent AntioxidantsMohamed Adardour0Marouane Ait Lahcen1Mehdi Oubahmane2Walid Ettahiri3Ismail Hdoufane4Hafida Bouamama5Mohammed M. Alanazi6Driss Cherqaoui7Mustapha Taleb8Elena Zaballos Garcia9Abdesselam Baouid10Molecular Chemistry Laboratory, Department of Chemistry, Semlalia Faculty of Sciences, 2390, Cadi Ayyad University, Marrakech 40001, MoroccoMolecular Chemistry Laboratory, Department of Chemistry, Semlalia Faculty of Sciences, 2390, Cadi Ayyad University, Marrakech 40001, MoroccoMolecular Chemistry Laboratory, Department of Chemistry, Semlalia Faculty of Sciences, 2390, Cadi Ayyad University, Marrakech 40001, MoroccoMolecular Chemistry Laboratory, Department of Chemistry, Semlalia Faculty of Sciences, 2390, Cadi Ayyad University, Marrakech 40001, MoroccoMolecular Chemistry Laboratory, Department of Chemistry, Semlalia Faculty of Sciences, 2390, Cadi Ayyad University, Marrakech 40001, MoroccoLaboratory of Sustainable Development and Health Research, Faculty of Sciences and Techniques, Cadi Ayyad University, Marrakech 40000, MoroccoDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaMolecular Chemistry Laboratory, Department of Chemistry, Semlalia Faculty of Sciences, 2390, Cadi Ayyad University, Marrakech 40001, MoroccoLaboratory of Engineering, Electrochemistry, Modeling and Environment, Faculty of Sciences, Sidi Mohamed Ben Abdellah University, Fez 30000, MoroccoDepartment of Organic Chemistry, Faculty of Pharmacy, University of Valencia, Ave. Vte. Andres Estelles s/n, 46100 Valencia, SpainMolecular Chemistry Laboratory, Department of Chemistry, Semlalia Faculty of Sciences, 2390, Cadi Ayyad University, Marrakech 40001, MoroccoIn the present study, we used benzimidazolone as a starting material to efficiently synthesize several hybrid compounds of pyrazole benzimidazolone derivatives by the 1,3-dipolar cycloaddition reaction. These compounds were obtained in average yields and were characterized by NMR (<sup>1</sup>H and <sup>13</sup>C) and HRMS analysis. The antioxidant activity of the synthesized compounds <b>5</b>(<b>a</b>–<b>c</b>) and <b>6</b>(<b>a</b>–<b>c</b>) was evaluated using in vitro reduction assays, including ferric reducing antioxidant power (FRAP) and total antioxidant capacity (TAC). The results indicated that products <b>5c</b>, <b>6b</b>, and <b>6c</b> exhibit higher antioxidant activity compared to the reference compounds and showed a remarkable ability to effectively remove the radical at IC<sub>50</sub> (14.00 ± 0.14, 12.47± 0.02, and 12.82 ± 0.10 µM, respectively) under the TAC assessment. Conversely, compound <b>6c</b> showed excellent activity at IC<sub>50</sub> (68.97 ± 0.26 µM) in the FRAP assay. We carried out molecular docking and dynamics simulations to investigate the binding mode and stability of <b>5c</b>, <b>6b</b>, and <b>6c</b> in the active site of human Peroxiredoxin 5. An ADMET study was conducted to determine the drug properties of the synthesized compounds.https://www.mdpi.com/1424-8247/16/12/1648pyrazolyl-benzimidazoloneantioxidant activityFRAPTACmolecular docking |
| spellingShingle | Mohamed Adardour Marouane Ait Lahcen Mehdi Oubahmane Walid Ettahiri Ismail Hdoufane Hafida Bouamama Mohammed M. Alanazi Driss Cherqaoui Mustapha Taleb Elena Zaballos Garcia Abdesselam Baouid Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants Pharmaceuticals pyrazolyl-benzimidazolone antioxidant activity FRAP TAC molecular docking |
| title | Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants |
| title_full | Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants |
| title_fullStr | Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants |
| title_full_unstemmed | Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants |
| title_short | Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants |
| title_sort | design synthesis molecular modeling and biological evaluation of novel pyrazole benzimidazolone derivatives as potent antioxidants |
| topic | pyrazolyl-benzimidazolone antioxidant activity FRAP TAC molecular docking |
| url | https://www.mdpi.com/1424-8247/16/12/1648 |
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