Adardour Mohamed, Ait Lahcen Marouane, Oubahmane Mehdi, Ettahiri Walid, Hdoufane Ismail, Bouamama Hafida, Alanazi Mohammed M, Cherqaoui Driss, Taleb Mustapha, Garcia Elena Zaballos, Baouid Abdesselam
Molecular Chemistry Laboratory, Department of Chemistry, Semlalia Faculty of Sciences, 2390, Cadi Ayyad University, Marrakech 40001, Morocco.
Laboratory of Engineering, Electrochemistry, Modeling and Environment, Faculty of Sciences, Sidi Mohamed Ben Abdellah University, Fez 30000, Morocco.
Pharmaceuticals (Basel). 2023 Nov 24;16(12):1648. doi: 10.3390/ph16121648.
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 (H and C) and HRMS analysis. The antioxidant activity of the synthesized compounds (-) and (-) was evaluated using in vitro reduction assays, including ferric reducing antioxidant power (FRAP) and total antioxidant capacity (TAC). The results indicated that products , , and exhibit higher antioxidant activity compared to the reference compounds and showed a remarkable ability to effectively remove the radical at IC (14.00 ± 0.14, 12.47± 0.02, and 12.82 ± 0.10 µM, respectively) under the TAC assessment. Conversely, compound showed excellent activity at IC (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 , , and in the active site of human Peroxiredoxin 5. An ADMET study was conducted to determine the drug properties of the synthesized compounds.
在本研究中，我们以苯并咪唑酮为起始原料，通过1,3 - 偶极环加成反应高效合成了几种吡唑苯并咪唑酮衍生物的杂化化合物。这些化合物的平均产率较高，并通过核磁共振（氢谱和碳谱）和高分辨质谱分析进行了表征。使用体外还原试验，包括铁还原抗氧化能力（FRAP）和总抗氧化能力（TAC），对合成化合物（-）和（-）的抗氧化活性进行了评估。结果表明，与参考化合物相比，产物、和表现出更高的抗氧化活性，并且在TAC评估下，在IC（分别为14.00±0.14、12.47±0.02和12.82±0.10μM）时显示出有效清除自由基的显著能力。相反，化合物在FRAP试验中在IC（68.97±0.26μM）时表现出优异的活性。我们进行了分子对接和动力学模拟，以研究、和在人过氧化物还原酶5活性位点的结合模式和稳定性。进行了ADMET研究以确定合成化合物的药物性质。
