The development of multifunctional drug for magnetic resonance imaging diagnosis that uses metallic complex liquid crystal compound

本研究主要研究液晶化合物（LC）的生物活性及其磁场和电场取向，以期开发新型金属配合物，并将其应用于磁共振成像诊断药物。我们揭示了以下几点。两种两亲性lc被认为通过抑制MCM2、细胞周期蛋白A、细胞周期蛋白B、CDK2、磷酸化cdk1 （Tyr15）和Cdc25的表达，延缓了人白血病单核细胞淋巴瘤U937细胞周期的s期进展。苯基嘧啶衍生物和氰联苯衍生物在A549人肺癌细胞中表现出细胞抑制作用，通过G1期阻滞抑制细胞生长。其中一种苯基嘧啶衍生物抑制A549的生长，对正常成纤维细胞无任何毒性。研究了16种液晶相关化合物对慢性髓性白血病细胞株K562的生物学活性。结果表明，2-（4-丁氧基苯基）-5-（4-羟基苯基）嘧啶和2-{4-（4-己氧基苯基）苯基}-5-羟基嘧啶在μM范围内对K562细胞有明显的生长抑制作用。此外，只有前者能诱导p38丝裂原活化蛋白激酶和c-Jun n-末端激酶的活化，以及K562细胞的凋亡。4-氰基-4′-（6-羟基己氧基）联苯（I-CN）和4-甲基-氧基-4′-（6-羟基己氧基）联苯（I-OMe）的等摩尔混合物对A549人肺癌细胞系的生长有较大的抑制作用，形成热致和溶致液晶相的能力比I-CN或I-OMe强5。我们目前正在研究新型金属络合物LCs的开发，这种LCs可以通过电场或磁场的外部刺激来调节，用于未来的药理学应用。

Focusing on the biological activities of liquid crystal compound (LC) and their magnetic and electric field orientation, the purpose of this study was to develop the novel metallic complex and apply as the diagnostic drug in magnetic resonance imaging.We revealed the following points.1. Two amphiphilic LCs were considered to delay S-phase progression in cell cycle of human leukemic monocyte lymphoma U937 cells, through inhibition of MCM2, cyclin A, cyclin B, CDK2, phospho-CDK1 (Tyr15) and Cdc25 expression.2. The phenylpyrimidine derivatives and cyanobiphenyl derivatives showed cytostatic effects, causing the suppression of cell growth through G1 phase arrest in A549 human lung cancer cells. One of the phenylpyrimidine derivatives inhibited A549 growth without any toxicity to normal fibroblasts.3. The biological activity of 16 liquid crystal-related compounds to a chronic myelogenous leukemia cell line, K562, was evaluated. As a result, two compounds, 2-(4-butoxyphenyl)-5-(4-hydroxyphenyl) pyrimidine and 2-{4-(4-hexyloxyphenyl) phenyl}-5-hydroxypyrimidine showed marked growth suppression of K562 cells at μM range. In addition, only the former compound induced the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and apoptosis of K562 cells.4. An equimolar mixture of 4-cyano-4'-(6-hydroxyhexyloxy) biphenyl (I-CN) and 4-methyl-oxy-4'-(6-hydroxyhexyloxy) biphenyl (I-OMe) exhibits larger suppressive effects on the growth of A549 human lung cancer cell line and shows higher ability to form thermotropic and lyotropic liquid-crystalline phases than I-CN or I-OMe.5. We are currently examining the development of novel metallic complex LCs which can be regulated by external stimulation by an electrical field or magnetic field for future pharmacological application.