The clinically utility of selective monoamine oxidase (MAO)‐B inhibitors in Parkinson disease is widely recognized due to significant improvement in altered motor function and long‐term benefit. Therefore, in the present study, a series of procaine‐imidazole was synthesized and subsequently evaluated for MAO‐A and MAO‐B inhibitory activity in an enzymatic assay. Comparative inhibitory activity suggest that, target compounds selectively inhibit MAO‐B, as compared to MAO‐A. Among the tested derivatives, compound 8 i (2‐(diethylamino)ethyl4‐(4‐(4‐fluorophenyl)‐2‐(4‐hydroxyphenyl)‐1H‐imidazol‐1‐yl)benzoate) selectively inhibited MAO‐B with IC₅₀ of 0.032±0.002 (selectivity index over MAO‐A=475). The anti‐Parkinson effect of compound 8 i was further evaluated in MPTP (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) induced animal model of PD. It has been found that, compound 8 i causes significant improvement in motor function of mice as revealed by motor behavioral assessment using the footprint and horizontal wire test. Compound 8 i also improved the level of anti‐oxidant enzymes in the striatum of animal brains. Our study demonstrated the development of procaine‐imidazole derivatives as potent and selective MAO‐B inhibitor as potential agent against PD.

中文翻译：

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发现新的普鲁卡因-咪唑衍生物作为单胺氧化酶-B抑制剂对帕金森氏病有潜在益处

选择性单胺氧化酶（MAO）-B抑制剂在帕金森氏病中的临床应用已得到广泛认可，这是由于运动功能改变和长期获益的显着改善。因此，在本研究中，合成了一系列普鲁卡因-咪唑，随后在酶促测定中评估了其对MAO-A和MAO-B的抑制活性。比较抑制活性表明，与MAO-A相比，目标化合物选择性抑制MAO-B。在测试的衍生物中，化合物8 i（2-（二乙氨基）乙基4-（4-（4-氟苯基）-2-（4-羟基苯基）-1H-咪唑-1-基）苯甲酸酯）通过IC选择性抑制MAO-B ₅₀ of 0.032±0.002（在MAO-A上的选择性指数= 475）。化合物8 i的抗帕金森效应在MPTP（1-甲基-4-苯基-1,2,3,6-四氢吡啶）诱导的PD动物模型中进行了进一步评估。已经发现，化合物8 i引起小鼠运动功能的显着改善，如通过使用足迹和水平导线测试进行的运动行为评估所揭示的。化合物8 i还改善了动物脑纹状体中抗氧化酶的水平。我们的研究证明了普鲁卡因-咪唑衍生物作为有效的PD抑制剂和选择性MAO-B抑制剂的发展潜力。