Discovery of small-molecule compounds and natural products against Parkinson's disease: Pathological mechanism and
Zhichao Zhong1, Xingrui He2, Jiamin Ge1
1College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, PR China; School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, PR China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicine, Engineering Laboratory of Development and Application of Traditional Chinese Medicine, Collaborative Innovation Center of Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, PR China.
Abstract:
Parkinson's disease (PD) is the second common neurodegenerative disease characterized by movement disorder. The symptoms of PD harm both the physical and mental health of patients. However, the current treatment strategies for PD only alleviate the symptoms but cannot recover the degenerative process of dopaminergic neurons. Therefore, it is necessary to develop novel and safe drugs for the treatment of PD. In this review, we comprehensively summarized the detailed pathological mechanisms and potential drugable targets of PD. The approved anti-PD drugs in clinical use and the drug candidates under clinical trials were also listed. More importantly, the compounds in the drug discovery phase with in vivo anti-PD activities in the recent two decades (2000-2020) were summarized. The structure-activity relationships (SARs) were also analyzed. Additionally, we predicted all the reviewed compounds' blood-brain barrier (BBB) permeability and statistically analyzed their pharmacological targets and in vivo anti-PD testing models. It is hoped that this review can provide practical information for researchers in the field of anti-PD drug discovery and promote their research work.
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