Beatson Institute for Cancer Research, Garscube Estate, Switchback Road Glasgow G61 1BD, UK.
Cell Commun Signal. 2013 Aug 14;11:58. doi: 10.1186/1478-811X-11-58.
Cucurbitacins are a class of triterpenoid natural compounds with potent bioactivities that led to their use as traditional remedies, and which continue to attract considerable attention as chemical biology tools and potential therapeutics. One obvious target is the actin-cytoskeleton; treatment with cucurbitacins results in cytoskeletal rearrangements that impact upon motility and cell morphology.
Cucurbitacin reacted with protein cysteine thiols as well as dithiothreitol, and we propose that the cucurbitacin mechanism of action is through broad protein thiol modifications that could result in inhibition of numerous protein targets. An example of such a target protein is Cofilin1, whose filamentous actin severing activity is inhibited by cucurbitacin conjugation.
The implications of these results are that cucurbitacins are unlikely to be improved for selectivity by medicinal chemistry and that their use as chemical biology probes to analyse the role of specific signalling pathways should be undertaken with caution.
葫芦素是一类具有强大生物活性的三萜类天然化合物，曾被用作传统药物，并且作为化学生物学工具和潜在治疗药物继续引起广泛关注。一个明显的靶点是肌动蛋白细胞骨架；葫芦素处理会导致影响运动和细胞形态的细胞骨架重排。
葫芦素与蛋白质半胱氨酸巯基以及二硫苏糖醇反应，我们提出葫芦素的作用机制是通过广泛的蛋白质巯基修饰，从而可能抑制许多蛋白质靶标。这样的靶标蛋白的一个例子是 Cofilin1，其丝状肌动蛋白的切断活性被葫芦素结合所抑制。
这些结果表明，葫芦素不太可能通过药物化学进行选择性改良，并且应该谨慎使用它们作为化学生物学探针来分析特定信号通路的作用。
