Nair Jerald J, van Staden Johannes, Bastida Jaume
Departament de Productes Naturals, Biologia Vegetal i Edafologia, Facultat de Farmàcia, Universitat de Barcelona, Av. Diagonal 643, Barcelona - 08028, Spain.
Curr Med Chem. 2016;23(2):161-85. doi: 10.2174/0929867323666151118121124.
The Amaryllidaceae occupies a privileged status amongst medicinal plants in having delivered the Alzheimer's drug galanthamine to the clinical market. Following its resounding success, there have been several positive indicators for the emergence of an anticancer drug from the family due to the potent antiproliferative activities manifested by several of its alkaloid constituents. Of these, the phenanthridones such as pancratistatin hold most promise as potential chemotherapeutics having succumbed to various phases of clinical trials. Other cytotoxic targets of the Amaryllidaceae are to be found within the lycorane and crinane groups, as exemplified by crinine and lycorine. Although the molecular targets of these alkaloids still remain elusive, much effort has gone into understanding their mode of action in cancer cells. Recent findings have shown that the apoptotic pathway may be a key factor in cancer cell death instigated by Amaryllidaceae alkaloids. As such, this review seeks to: (a) examine the apoptotic effects of Amaryllidaceae alkaloids in cancer cells; (b) explore the molecular basis to these effects; and (c) provide a pharmacophoric rationale in support of these activities.
石蒜科在药用植物中占据着特殊地位，因为它已将治疗阿尔茨海默病的药物加兰他敏推向临床市场。继其取得巨大成功之后，由于该科几种生物碱成分表现出强大的抗增殖活性，出现一种抗癌药物的迹象颇为积极。其中，诸如 pancratistatin 等菲啶酮作为潜在的化疗药物最具前景，已进入临床试验的各个阶段。石蒜科的其他细胞毒性靶点存在于石蒜烷和水仙烷类化合物中，如 crinine 和 lycorine 所示。尽管这些生物碱的分子靶点仍不明确，但人们已付出诸多努力来了解它们在癌细胞中的作用方式。最近的研究结果表明，凋亡途径可能是石蒜科生物碱引发癌细胞死亡的关键因素。因此，本综述旨在：(a) 研究石蒜科生物碱对癌细胞的凋亡作用；(b) 探究这些作用的分子基础；(c) 提供支持这些活性的药效团原理。
