Müller W E, Zahn R K, Gasić M J, Dogović N, Maidhof A, Becker C, Diehl-Seifert B, Eich E
Comp Biochem Physiol C Comp Pharmacol Toxicol. 1985;80(1):47-52. doi: 10.1016/0742-8413(85)90130-6.
A main metabolic product of the sponge Dysidea avara was isolated and purified and subsequently identified as avarol by applying a series of analytical techniques, e.g. [13C]NMR, [1H]NMR and i.r. spectroscopy. This sesquiterpenoid hydroquinone was found to possess strong cytostatic activity. Using the L5178y mouse lymphoma cell system in vitro (roller tube assays) avarol reduced cell growth to 50% at a concentration of 0.9 microM. Avarol treated cells did not show "unbalanced growth". Avarol interfered with mitotic processes, preventing telophase formation. Incorporation studies with precursors for DNA, RNA, protein and glycoprotein syntheses revealed increased incorporation rates in response to avarol treatment. From these results and further autoradiographical experiments it is suggested that inhibition of cell growth is due to changes of the intracellular pools and/or alterations of the permeability properties of the cell membrane for the precursors. Avarol diacetate caused the same cytostatic effect as avarol.
从海绵阿氏软海绵(Dysidea avara)中分离并纯化出一种主要代谢产物,随后通过一系列分析技术,如[13C]核磁共振(NMR)、[1H]核磁共振(NMR)和红外光谱对其进行鉴定,确定为阿伐他汀。发现这种倍半萜对苯二酚具有很强的细胞抑制活性。在体外使用L5178y小鼠淋巴瘤细胞系统(滚管试验),阿伐他汀在浓度为0.9微摩尔时可将细胞生长降低至50%。经阿伐他汀处理的细胞未显示出“生长失衡”。阿伐他汀干扰有丝分裂过程,阻止末期形成。对DNA、RNA、蛋白质和糖蛋白合成前体的掺入研究表明,经阿伐他汀处理后掺入率增加。从这些结果以及进一步的放射自显影实验表明,细胞生长的抑制是由于细胞内池的变化和/或细胞膜对前体通透性的改变。阿伐他汀二乙酸酯产生与阿伐他汀相同的细胞抑制作用。