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石蒜科生物碱的细胞毒性研究

Cytotoxicity studies of lycorine alkaloids of the Amaryllidaceae.

作者信息

Nair Jerald J, van Staden Johannes

出版信息

Nat Prod Commun. 2014 Aug;9(8):1193-210.

Abstract

The plant family Amaryllidaceae is renowned for its unique alkaloid constituents which possess a significant array of structural diversity. Several of these alkaloids are known for their interesting biological properties, of which galanthamine and pancratistatin have acquired a privileged status due to their relevance in the pharmaceutical arena. In particular, galanthamine represents the first prescription drug emanating from the Amaryllidaceae after its approval by the FDA in 2001 for the treatment of Alzheimer's disease. Following on this commercial success there have been sustained projections for the emergence of an anticancer agent related to pancratistatin due to the potency, selectivity, low toxicity and high tolerability typifying targets of this series of alkaloids. The lycorine series of alkaloids have also garnered widespread interest as cytotoxic agents and were amongst the earliest of the Amaryllidaceae constituents to exhibit such activity. To date over 100 of such naturally-occurring or synthetically-derived alkaloids have been screened for cytotoxic effects against a number of cancer cell lines. This survey examines the cytotoxic properties of lycorine alkaloids, highlights the outcomes of structure-activity relationship orientated studies and affords plausible insights to the mechanistic rationale behind these effects.

摘要

石蒜科植物家族以其独特的生物碱成分而闻名,这些生物碱具有显著的结构多样性。其中几种生物碱因其有趣的生物学特性而闻名,由于加兰他敏和潘克拉他汀在制药领域的相关性,它们已获得特殊地位。特别是,加兰他敏是2001年美国食品药品监督管理局(FDA)批准用于治疗阿尔茨海默病后,第一种源自石蒜科植物的处方药。继这一商业成功之后,由于这一系列生物碱的典型靶点具有效力、选择性、低毒性和高耐受性,人们持续预测会出现一种与潘克拉他汀相关的抗癌药物。石蒜碱系列生物碱作为细胞毒性剂也引起了广泛关注,并且是最早表现出这种活性的石蒜科植物成分之一。迄今为止,已经对100多种此类天然存在或合成衍生的生物碱针对多种癌细胞系进行了细胞毒性作用筛选。本综述研究了石蒜碱生物碱的细胞毒性特性,突出了构效关系导向研究的结果,并对这些作用背后的机制原理提供了合理的见解。

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