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天然异喹啉生物碱:药理学特性及对复杂疾病的多靶点作用潜力

Natural isoquinoline alkaloids: Pharmacological features and multi-target potential for complex diseases.

作者信息

Plazas Erika, Avila M Mónica C, Muñoz Diego R, Cuca S Luis E

机构信息

Universidad Nacional de Colombia, Sede Bogotá, Facultad de Ciencias, Departamento de Química, Grupo de Investigación en Productos Naturales Vegetales Bioactivos, Av Cr 30. #45-03, 111321 Bogotá, Colombia.

Universidad Nacional de Colombia, Sede Bogotá, Facultad de Ciencias, Departamento de Química, Grupo de Investigación en Productos Naturales Vegetales Bioactivos, Av Cr 30. #45-03, 111321 Bogotá, Colombia.

出版信息

Pharmacol Res. 2022 Mar;177:106126. doi: 10.1016/j.phrs.2022.106126. Epub 2022 Feb 10.

Abstract

Complex diseases such as neurodegenerative disorders and cancer constitute a growing public health problem due to the rising incidence and lack in effective therapies. Since pharmacotherapy based on a single target has been insufficient for drug development in complex diseases, the emerging multi-target approach is a promising strategy for the search of new drug candidates. Plant-derived isoquinoline alkaloids comprise a vast source of multimodal agents with unique structural diversity, and variated range of pharmacological activities. This review offers an exhaustive compilation of the pharmacological relevance and multi-target potential of natural isoquinolines, emphasizing their features and promising activity in complex diseases such as Alzheimer, Parkinson, and Cancer. Selected examples were discussed in depth to illustrate the most relevant structural motifs and their possible relationship with the multimodal activity offering a comprehensive baseline in the search and optimization of isoquinoline scaffolds with polypharmacological potential for complex diseases.

摘要

诸如神经退行性疾病和癌症等复杂疾病,由于发病率不断上升且缺乏有效治疗方法,正构成日益严重的公共卫生问题。由于基于单一靶点的药物治疗在复杂疾病的药物开发中已显不足,新兴的多靶点方法是寻找新候选药物的一种有前景的策略。植物来源的异喹啉生物碱包含大量具有独特结构多样性和多种药理活性的多模式药物。本综述详尽汇编了天然异喹啉的药理学相关性和多靶点潜力,强调了它们在诸如阿尔茨海默病、帕金森病和癌症等复杂疾病中的特征和有前景的活性。深入讨论了选定的实例,以说明最相关的结构基序及其与多模式活性的可能关系,为寻找和优化具有治疗复杂疾病多药理学潜力的异喹啉支架提供全面的基线。

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