Kostova Irena
Department of Chemistry, Faculty of Pharmacy, Medical University, 2 Dunav St., Sofia 1000, Bulgaria.
Curr Med Chem Anticancer Agents. 2005 Jan;5(1):29-46. doi: 10.2174/1568011053352550.
Coumarins, an old class of compounds, are naturally occurring benzopyrene derivatives. A lot of coumarins have been identified from natural sources, especially green plants. The pharmacological and biochemical properties and therapeutic applications of simple coumarins depend upon the pattern of substitution. Coumarins have attracted intense interest in recent years because of their diverse pharmacological properties. Among these properties, their cytotoxic effects were most extensively examined. In this review, their broad range of effects on the tumors as shown by various in vitro and in vivo experiments and clinical studies are discussed. Hence, these cytotoxic coumarins represent an exploitable source of new anticancer agents, which might also help addressing side-toxicity and resistance phenomena. These natural compounds have served as valuable leads for further design and synthesis of more active analogues. In this review, plant derived coumarins and their synthetic analogues were systematically evaluated based on their plant origin, structure-activity relationship and anticancer efficacy. Owing the their diverse effects and inconclusive results from different in vitro studies, the mechanism of their action is not yet fully understood and correlation of effects with chemical structures is not conclusive at the moment. It is the objective of this review to summarize experimental data for different coumarins, used as cytotoxic agents, because promising data have been reported for a series of these agents. Yet, the results from different coumarins with various tumor lines are contradictory in part. We therefore conclude that there is still a long way to go until we know which cytotoxic agent will clinically be suitable for what tumor entity for treatment. Their ability to bind metal ions represents an additional means of modulating their pharmacological responses.
香豆素是一类古老的化合物，是天然存在的苯并芘衍生物。已从天然来源，尤其是绿色植物中鉴定出许多香豆素。简单香豆素的药理、生化特性及治疗应用取决于其取代模式。近年来，香豆素因其多样的药理特性而备受关注。在这些特性中，其细胞毒性作用得到了最广泛的研究。在本综述中，将讨论各种体外和体内实验及临床研究显示的它们对肿瘤的广泛作用。因此，这些具有细胞毒性的香豆素是新抗癌药物的可开发来源，这也可能有助于解决副作用和耐药现象。这些天然化合物为进一步设计和合成更具活性的类似物提供了有价值的线索。在本综述中，基于植物来源、构效关系和抗癌功效，对植物来源的香豆素及其合成类似物进行了系统评估。由于它们的作用多样且不同体外研究结果尚无定论，其作用机制尚未完全明确，目前其作用与化学结构的相关性也尚无定论。本综述的目的是总结用作细胞毒性剂的不同香豆素的实验数据，因为已报道了一系列此类药物的有前景的数据。然而，不同香豆素对各种肿瘤细胞系的结果部分相互矛盾。因此，我们得出结论，在了解哪种细胞毒性剂临床上适用于哪种肿瘤实体进行治疗之前，仍有很长的路要走。它们结合金属离子的能力是调节其药理反应的另一种方式。
