Abstract From camptothecin to vinblastine, plant alkaloids continue to capture the imagination of scientists as a valuable source of anticancer drugs. Given that they are also amongst the most common secondary metabolites encountered in plants, the number of alkaloid entities subjected to cytotoxicity evaluations now runs into several thousands. Interest in the plant family Amaryllidaceae has been persistent owing to the potent cytotoxic activities of several of its isoquinoline alkaloid principles. This survey is an indepth account of such properties discernible for tazettine alkaloids belonging to the minor alkaloid groups of the Amaryllidaceae. Eleven of such compounds have up to now been screened against around 50 cancer cell lines which may be classified into nearly 20 different types of cancers. Although the activities in most instances were moderate to mild, notable responses were observed against some leukemia, adenocarcinoma, lymphoma and glioblastoma cell lines. In fact, pretazettine (ED50 0.3 μg/mL) was amongst the most potent of all Amaryllidaceae alkaloids screened against the human Molt4 T-lymphoma cell line. To most accounts, the parent compounds (such as tazettine and pretazettine) with their distinct ring systems and substitution patterns exhibit the best activities, offering little space for structural adjustments via semi-synthetic operations. Several avenues have been probed in attempts to elucidate the mechanisms by which tazettine alkaloids manifest their cytotoxic effects including, inhibition of protein synthesis, apoptosis and efflux pump interactions, the first of which to date offers the most profound insights.

中文翻译：

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植物家族石蒜科的细胞毒性 tazettine 生物碱

摘要 从喜树碱到长春碱，植物生物碱作为抗癌药物的宝贵来源不断吸引着科学家的想象力。鉴于它们也是植物中最常见的次生代谢物之一，因此进行细胞毒性评估的生物碱实体的数量现在达到数千种。由于其几种异喹啉生物碱成分的强效细胞毒活性，人们对石蒜科植物的兴趣一直存在。本次调查深入介绍了属于石蒜科次要生物碱群的 tazettine 生物碱的此类特性。迄今为止，已经针对大约 50 种癌细胞系筛选了 11 种此类化合物，这些癌细胞系可分为近 20 种不同类型的癌症。尽管在大多数情况下的活性是中度至轻度，但观察到对某些白血病、腺癌、淋巴瘤和胶质母细胞瘤细胞系的显着反应。事实上，pretazettine (ED50 0.3 μg/mL) 是针对人 Molt4 T 淋巴瘤细胞系筛选的所有石蒜科生物碱中最有效的。在大多数情况下，具有独特环系统和取代模式的母体化合物（如他泽汀和 pretazettine）表现出最好的活性，通过半合成操作进行结构调整的空间很小。已经探索了几种途径以试图阐明他泽汀生物碱显示其细胞毒性作用的机制，包括抑制蛋白质合成、细胞凋亡和外排泵相互作用，其中第一个提供了迄今为止最深刻的见解。