Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines, CIRM, University of Liège, Avenue Hippocrate 15, 4000 Liège, Belgium.
Laboratory of Biology of Tumor and Development, GIGA/CIRM, University of Liège, Avenue Hippocrate 15, 4000 Liège, Belgium.
Molecules. 2023 Jan 25;28(3):1197. doi: 10.3390/molecules28031197.
Vent., an endemic plant from the Mascarene Islands, was investigated following its antiplasmodial potentialities highlighted during a previous screening. Three clerodane diterpene compounds were isolated and identified as being responsible for the antiplasmodial activity of the leaves of the plant: caseamembrin T (), corybulosin I (), and isocaseamembrin E (), which exhibited half maximal inhibitory concentrations (IC) of 0.25 to 0.51 µg/mL. These compounds were tested on two other parasites, and , to identify possible selectivity in one of them. Although these products possess both antileishmanial and antitrypanosomal properties, they displayed selectivity for the malaria parasite, with a selectivity index between 6 and 12 regarding antitrypanosomal activity and between 25 and 100 regarding antileishmanial activity. These compounds were tested on three cell lines, breast cancer cells MDA-MB-231, pulmonary adenocarcinoma cells A549, and pancreatic carcinoma cells PANC-1, to evaluate their selectivity towards . This has not enabled us to establish selectivity for , but has revealed the promising activity of compounds - (IC < 2 µg/mL), particularly against pancreatic carcinoma cells (IC < 1 µg/mL). The toxicity of the main compound, caseamembrin T (), was then evaluated on zebrafish embryos to extend our cytotoxicity study to normal, non-cancerous cells. This highlighted the non-negligible toxicity of caseamembrin T ().
万特(Vent.)是一种来自马斯克林群岛的特有植物,在先前的筛选中因其抗疟原虫特性而受到关注。从该植物的叶子中分离并鉴定出三种 clerodane 二萜化合物,它们是植物抗疟原虫活性的主要成分:桉脂素 T()、考布素 I()和异桉脂素 E(),它们的半数最大抑制浓度(IC)分别为 0.25 至 0.51 µg/mL。这些化合物在另外两种寄生虫,和 中进行了测试,以确定其中一种可能的选择性。尽管这些产品具有抗利什曼原虫和抗锥虫的特性,但它们对疟原虫表现出选择性,其抗锥虫活性的选择性指数在 6 到 12 之间,抗利什曼原虫活性的选择性指数在 25 到 100 之间。这些化合物在三种细胞系,乳腺癌细胞 MDA-MB-231、肺腺癌细胞 A549 和胰腺癌细胞 PANC-1 上进行了测试,以评估它们对 的选择性。这不能确定对 的选择性,但显示了化合物 -(IC < 2 µg/mL)的有希望的活性,特别是对胰腺癌细胞(IC < 1 µg/mL)。然后,主要化合物桉脂素 T()在斑马鱼胚胎上的毒性进行了评估,以将我们的细胞毒性研究扩展到正常的非癌细胞。这突出了桉脂素 T()的不可忽视的毒性。