2. Academic Validation
  3. Neuroprotective effects of benzyloxy substituted small molecule monoamine oxidase B inhibitors in Parkinson's disease

Neuroprotective effects of benzyloxy substituted small molecule monoamine oxidase B inhibitors in Parkinson's disease

  • Bioorg Med Chem. 2016 Nov 15;24(22):5929-5940. doi: 10.1016/j.bmc.2016.09.050.
Zhimin Wang 1,  Jiajia Wu 1,  Xuelian Yang 1,  Pei Cai 1,  Qiaohong Liu 1,  Kelvin D G Wang 1,  Lingyi Kong 2,  Xiaobing Wang 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China.
  • 2 State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. Electronic address: [email protected].
  • 3 State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People's Republic of China. Electronic address: [email protected].
PMID: 27692996 DOI: 10.1016/j.bmc.2016.09.050
Abstract

The benzyloxy substituted small molecules are well-known highly potent Monoamine Oxidase B inhibitors, but their therapeutic potential against Parkinson's disease have not been investigated in detail. In this paper, a series of representative benzyloxy substituted derivatives were synthesized and evaluated for MAO-A/B inhibition. In addition, their neuroprotective effects were investigated in 6-OHDA- and rotenone-treated PC12 cells. It was observed that most of the compounds exhibited a marked increase in survival of PC12 cells which treated with the neurotoxins. Among them, 13 exhibited remarkable and balanced neuroprotective potency. The protective effects of 13 against neurotoxins-induced Apoptosis were confirmed with flow cytometry and staining methods. Furthermore, 13 also showed good BBB permeability and low toxicity according to in vitro BBB prediction and in vivo acute toxicity test. The results indicated that 13 is an effective and promising candidate to be further developed as disease-modifying drug for Parkinson's disease therapy.

Keywords

Apoptosis; BBB permeability; Monoamine oxidase; Neuroprotection; Parkinson’s disease.

Figures
Products