2. Academic Validation
  3. Discovery of novel 2-hydroxyl-4-benzyloxybenzyl aniline derivatives as potential multifunctional agents for the treatment of Parkinson's disease

Discovery of novel 2-hydroxyl-4-benzyloxybenzyl aniline derivatives as potential multifunctional agents for the treatment of Parkinson's disease

  • Eur J Med Chem. 2023 Mar 5;249:115142. doi: 10.1016/j.ejmech.2023.115142.
Zhongcheng Cao 1,  Xianwu Fu 2,  Xingyue Wang 2,  Tianlong Zhang 2,  Lei Zhong 3,  Qian Xia 3,  Jiang Zhu 4
Affiliations

Affiliations

  • 1 School of Pharmacy, North Sichuan Medical College, Nanchong, 637000, China. Electronic address: [email protected].
  • 2 School of Pharmacy, North Sichuan Medical College, Nanchong, 637000, China.
  • 3 Sichuan Key Laboratory of Medical Imaging, Nanchong, 637000, China.
  • 4 Sichuan Key Laboratory of Medical Imaging, School of Pharmacy and Nanchong Key Laboratory of MRI Contrast Agent, North Sichuan Medical College, Nanchong, 637000, China.
PMID: 36716641 DOI: 10.1016/j.ejmech.2023.115142
Abstract

To discover novel multifunctional agents for the treatment of Parkinson's disease, a series of 2-hydroxyl-4-benzyloxybenzyl aniline derivatives was designed, synthesized and evaluated. The biological screening indicated that representative compound 6h possessed excellent MAO-B inhibition (IC50 = 0.014 μM), high antioxidant activity (ORAC = 2.14 Trolox equivalent), good metal chelating ability, appropriate BBB permeability and significant neuroprotective effect. Additionally, 6h exhibited great ability to alleviate the neuroinflammtion by suppressing the activation of NF-κB pathway in vitro. Furthermore, 6h can also ameliorate MPTP induced Parkinson's disease symptoms in mice by improving the dopamine level and repressing oxidative damage. These results indicated that compound 6h was a promising candidate for further development against PD.

Keywords

2-hydroxyl-4-benzyloxybenzyl aniline derivatives; Anti-neuroinflammatory agents; Antioxidants; MAO-B inhibitors; Multifunctional anti-PD agents; Parkinson's disease.

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