Zhang Jinling, Jiang Peng, Wang Shuping, Li Mengmeng, Hao Zhichao, Guan Wei, Pan Juan, Wu Jiatong, Zhang Yiqiang, Li Hua, Chen Lixia, Yang Bingyou, Liu Yan
Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin 150040, China; Research Institute of Medicine & Pharmacy, Qiqihar Medical University, Qiqihar 161006, China.
Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin 150040, China.
Bioorg Chem. 2024 Dec;153:107819. doi: 10.1016/j.bioorg.2024.107819. Epub 2024 Sep 13.
Neurodegenerative diseases (NDs) represent a hallmark of numerous incapacitating and untreatable conditions, the incidence of which is escalating swiftly, exemplified by Alzheimer's disease and Parkinson's disease. There is an urgent necessity to create pharmaceuticals that exhibit high efficacy and minimal toxicity in order to address these debilitating diseases. The structural complexity and diversity of natural products confer upon them a broad spectrum of biological activities, thereby significantly contributing to the history of drug discovery. Nevertheless, natural products present challenges in drug discovery, including time-consuming separation processes, low content, low bioavailability, and other related issues. To address these challenges, numerous analogs of natural products have been synthesized. This methodology enables the rapid synthesis of analogs of natural products with the potential to serve as lead compounds for drug development, thereby paving the way for the discovery of novel pharmaceuticals. This paper provides a summary of 127 synthetic analogues featuring various natural product structures, including flavonoids, alkaloids, coumarins, phenylpropanoids, terpenoids, polyphenols, and amides. The compounds are categorized based on their efficacy in treating various diseases. Furthermore, this article delves into the structure-activity relationship (SAR) of certain analogues, offering a thorough point of reference for the systematic development of pharmaceuticals aimed at addressing neurodegenerative conditions.
神经退行性疾病(NDs)是众多使人丧失能力且无法治愈的疾病的标志,其发病率正在迅速上升,阿尔茨海默病和帕金森病就是例证。迫切需要研发出高效且低毒的药物来应对这些使人衰弱的疾病。天然产物的结构复杂性和多样性赋予它们广泛的生物活性,从而对药物发现的历史做出了重大贡献。然而,天然产物在药物发现中存在挑战,包括耗时的分离过程、含量低、生物利用度低以及其他相关问题。为应对这些挑战,人们合成了许多天然产物类似物。这种方法能够快速合成具有作为药物开发先导化合物潜力的天然产物类似物,从而为新型药物的发现铺平道路。本文总结了127种具有各种天然产物结构的合成类似物,包括黄酮类、生物碱类、香豆素类、苯丙素类、萜类、多酚类和酰胺类。这些化合物根据其治疗各种疾病的功效进行分类。此外,本文深入探讨了某些类似物的构效关系(SAR),为系统开发旨在治疗神经退行性疾病的药物提供了全面的参考依据。