UCIBIO, REQUIMTE, Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Laboratory of Organic and Pharmaceutical Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Molecules. 2019 Jan 23;24(3):409. doi: 10.3390/molecules24030409.
Following our previous work on the antitumor activity of acetylated flavonosides, a new acetylated xanthonoside, 3,6-bis(2,3,4,6-tetra--acetyl-β-glucopyranosyl)xanthone (), was synthesized and discovered as a potent inhibitor of tumor cell growth. The synthesis involved the glycosylation of 3,6-di-hydroxyxanthone () with acetobromo-α-d-glucose. Glycosylation with silver carbonate decreased the amount of glucose donor needed, comparative to the biphasic glycosylation. Xanthone showed a potent anti-growth activity, with GI < 1 μM, in human cell lines of breast, lung, and glioblastoma cancers. Current treatment for invasive brain glioma is still inadequate and new agents against glioblastoma with high brain permeability are urgently needed. To overcome these issues, xanthone was encapsulated in a liposome. To increase the well-known low stability of these drug carriers, a proliposome formulation was developed using the spray drying method. Both formulations were characterized and compared regarding three months stability and in vitro anti-growth activity. While the proliposome formulation showed significantly higher stability, it was at the expense of losing its biocompatibility as a drug carrier in higher concentrations. More importantly, the new xanthone was still able to inhibit the growth of glioblastoma cells after liposome formulation.
在我们之前关于乙酰化黄酮类化合物抗肿瘤活性的研究工作之后，我们合成了一种新的乙酰化黄酮苷，即 3,6-双（2,3,4,6-四-O-乙酰基-β-吡喃葡萄糖基）呫吨酮（），并发现它是一种强效的肿瘤细胞生长抑制剂。该合成涉及 3,6-二羟基呫吨酮（）与乙酰溴-α-D-葡萄糖的糖苷化反应。与两相糖苷化相比，使用碳酸银进行糖苷化反应可以减少葡萄糖供体的用量。呫吨酮 显示出很强的抗生长活性，在乳腺癌、肺癌和神经胶质瘤的人类细胞系中 GI < 1 μM。目前，侵袭性脑胶质瘤的治疗仍然不足，迫切需要具有高脑通透性的新的神经胶质瘤治疗药物。为了克服这些问题，我们将呫吨酮包封在脂质体中。为了提高这些药物载体众所周知的低稳定性，我们使用喷雾干燥法开发了一种前脂质体制剂。对两种制剂进行了表征，并就三个月的稳定性和体外抗生长活性进行了比较。虽然前脂质体制剂的稳定性显著提高，但这是以更高浓度时失去其作为药物载体的生物相容性为代价的。更重要的是，新的呫吨酮 在脂质体制剂后仍能抑制神经胶质瘤细胞的生长。
