Kreuter M H, Bernd A, Holzmann H, Müller-Klieser W, Maidhof A, Weissmann N, Kljajić Z, Batel R, Schröder H C, Müller W E
Abteilung Angewandte Molekularbiologie, Universität, Mainz, Bundesrepublik Deutschland.
Z Naturforsch C J Biosci. 1989 Jul-Aug;44(7-8):680-8. doi: 10.1515/znc-1989-7-822.
(+/-)-Aeroplysinin-1, an optically active 1,2-dihydroarene-1,2-diol, was isolated from the marine sponges Verongia aerophoba (+-isomer) and Ianthella ardis (- -isomer). For the experiments presented we used the +-isomer from Verongia aerophoba. Here we describe the hitherto unknown biological and pharmacological property of this compound to display pronounced anticancer activity against L5178y mouse lymphoma cells (ED50: 0.5 microM). Friend erythroleukemia cells (ED50: 0.7 microM), human mamma carcinoma cells (ED50: 0.3 microM) and human colon carcinoma cells (ED50: 3.0 microM) in vitro. Furthermore, aeroplysinin caused a preferential inhibition of [3H]thymidine (dThd) incorporation rates in L5178y mouse lymphoma cells if compared with murine spleen lymphocytes in vitro. At concentrations between 1.1 and 28.5 microM, the [3H]dThd incorporation rates in L5178y cells were suppressed to 28%-0% but only to 78%-18% in murine spleen lymphocytes. The same differential effect in vitro was found with the following epithelial cells: 14.70 microM of the compound were required to inhibit normal human fibroblasts to 50%, but only 2.9 microM in the assays with human malign keratinocytes or malignant melanoma cells to observe the same inhibitory effect. Moreover, aeroplysinin-1 displayed antileukemic activity in vivo using the L5178y cell/NMRI mouse system; administered at a dose of 50 mg/kg for five consecutive days, the T/C (%) value was determined to be 338. Preliminary toxicology studies revealed an acute LD50 of 202 mg/kg and a subacute LD50 of 150 mg/kg. Aeroplysinin-1 is neither a direct mutagen nor a premutagen in the umu/Salmonella typhimurium test system.
（±）-Aeroplysinin-1是一种旋光性的1,2-二氢芳烃-1,2-二醇，从海洋海绵Verongia aerophoba（±异构体）和Ianthella ardis（--异构体）中分离得到。在本实验中，我们使用的是来自Verongia aerophoba的±异构体。在此，我们描述了该化合物迄今未知的生物学和药理学特性，即对L5178y小鼠淋巴瘤细胞（半数有效浓度：0.5微摩尔/升）、Friend红白血病细胞（半数有效浓度：0.7微摩尔/升）、人乳腺癌细胞（半数有效浓度：0.3微摩尔/升）和人结肠癌细胞（半数有效浓度：3.0微摩尔/升）具有显著的体外抗癌活性。此外，与体外的小鼠脾淋巴细胞相比，Aeroplysinin能优先抑制L5178y小鼠淋巴瘤细胞中[3H]胸苷（dThd）的掺入率。在1.1至28.5微摩尔/升的浓度范围内，L5178y细胞中[3H]dThd的掺入率被抑制至28% - 0%，而在小鼠脾淋巴细胞中仅被抑制至78% - 18%。在以下上皮细胞中也发现了相同的体外差异效应：抑制正常人成纤维细胞至50%需要14.70微摩尔/升的该化合物，但在用人恶性角质形成细胞或恶性黑色素瘤细胞进行的实验中，仅需2.9微摩尔/升就能观察到相同的抑制效果。此外，在L5178y细胞/NMRI小鼠系统中，Aeroplysinin-1在体内表现出抗白血病活性；连续五天以50毫克/千克的剂量给药，其T/C（%）值测定为338。初步毒理学研究显示，急性半数致死量为202毫克/千克，亚急性半数致死量为150毫克/千克。在umu/鼠伤寒沙门氏菌测试系统中，Aeroplysinin-1既不是直接诱变剂也不是前诱变剂。
