Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Institute of Clinical Physiology, National Research Council of Italy, CNR Research Area, 56124 Pisa, Italy.
Molecules. 2024 May 3;29(9):2127. doi: 10.3390/molecules29092127.
Neurodegeneration is a gradual decay process leading to the depletion of neurons in both the central and peripheral nervous systems, ultimately resulting in cognitive dysfunctions and the deterioration of brain functions, alongside a decline in motor skills and behavioral capabilities. Neurodegenerative disorders (NDs) impose a substantial socio-economic strain on society, aggravated by the advancing age of the world population and the absence of effective remedies, predicting a negative future. In this context, the urgency of discovering viable therapies is critical and, despite significant efforts by medicinal chemists in developing potential drug candidates and exploring various small molecules as therapeutics, regrettably, a truly effective treatment is yet to be found. Nitrogen heterocyclic compounds, and particularly those containing the indole nucleus, which has emerged as privileged scaffold, have attracted particular attention for a variety of pharmacological applications. This review analyzes the rational design strategy adopted by different research groups for the development of anti-neurodegenerative indole-based compounds which have the potential to modulate various molecular targets involved in NDs, with reference to the most recent advances between 2018 and 2023.
神经退行性变是一个渐进的衰退过程,导致中枢和外周神经系统中的神经元耗竭,最终导致认知功能障碍和脑功能恶化,同时运动技能和行为能力下降。神经退行性疾病(NDs)给社会带来了巨大的社会经济负担,加上世界人口老龄化和缺乏有效治疗方法的情况,预计未来情况会更加严峻。在这种情况下,发现可行的治疗方法至关重要,尽管药物化学家在开发潜在药物候选物和探索各种小分子作为治疗方法方面做出了巨大努力,但令人遗憾的是,仍然没有找到真正有效的治疗方法。氮杂环化合物,特别是含有吲哚核的化合物,已成为一种优势骨架,引起了广泛关注,可用于多种药理学应用。本文综述了不同研究小组为开发具有调节 NDs 中涉及的各种分子靶点潜力的基于吲哚的抗神经退行性化合物而采用的合理设计策略,参考了 2018 年至 2023 年之间的最新进展。