Discovery of novel 2-(4-(benzyloxy)-5-(hydroxyl) phenyl) benzothiazole derivatives as multifunctional MAO-B inhibitors for the treatment of Parkinson's disease

被引：5
作者：
Cao, Zhongcheng [1 ,4 ]
Wang, Xingyue [1 ]
Zhang, Tianlong [1 ]
Fu, Xianwu [1 ]
Zhang, Fan [1 ]
Zhu, Jiang [2 ,3 ,5 ,6 ]
机构：
[1] North Sichuan Med Coll, Sch Pharm, Nanchong, Peoples R China
[2] North Sichuan Med Coll, Sch Pharm, Sichuan Key Lab Med Imaging, Nanchong, Peoples R China
[3] North Sichuan Med Coll, Nanchong Key Lab MRI Contrast Agent, Nanchong, Peoples R China
[4] North Sichuan Med Coll, Sch Pharm, Nanchong 637000, Peoples R China
[5] North Sichuan Med Coll, Sch Pharm, Sichuan Key Lab Med Imaging, Nanchong 637000, Peoples R China
[6] North Sichuan Med Coll, Nanchong Key Lab MRI Contrast Agent, Nanchong 637000, Peoples R China
来源：
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2023年 / 38卷 / 01期
关键词：
Parkinson's disease; 2-(4-(benzyloxy)-5-(hydroxyl) phenyl) benzothiazole derivatives; MAO-B inhibitors; anti-neuroinflammatory agents; multifunctional anti-PD agents; MONOAMINE-OXIDASE; BIOLOGICAL EVALUATION; DESIGN; AGENTS; DOCKING; BEARING; ASSAY;
D O I：
10.1080/14756366.2022.2159957
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
To discover novel multifunctional agents for the treatment of Parkinson's disease, a series of 2-(4-(benzyloxy)-5-(hydroxyl) phenyl) benzothiazole derivatives was designed, synthesized and evaluated. The results revealed that representative compound 3h possessed potent and selective MAO-B inhibitory activity (IC50 = 0.062 mu M), and its inhibitory mode was competitive and reversible. Additionally, 3h also displayed excellent anti-oxidative effect (ORAC = 2.27 Trolox equivalent), significant metal chelating ability and appropriate BBB permeability. Moreover, 3h exhibited good neuroprotective effect and anti-neuroinflammtory ability. These results indicated that compound 3h was a promising candidate for further development against PD.
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页数：12
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