Preparation and biological activity of 6-benzylaminopurine derivatives in plants and human cancer cells
Preparation and biological activity of 6-benzylaminopurine derivatives in plants and human cancer cells
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DOI：
10.1016/j.bmc.2005.09.004
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发表时间：
2006-02-01
影响因子：
3.5
通讯作者：
Strnad, M
中科院分区：
文献类型：
--
作者：
Dolezal, K;Popa, I;Strnad, M
为了研究芳香族细胞分裂素的构效关系，比较了38种6-苄氨基嘌呤（BAP）衍生物在受体和细胞水平上的细胞分裂素活性以及CDK抑制和抗癌活性。这些化合物是由6-氯嘌呤与相应的取代苄胺缩合而成。大多数合成的衍生物在所有三个细胞分裂素生物测定（烟草愈伤组织，小麦衰老和苋属植物生物测定）中表现出高活性。在衰老生物测定中获得最高活性。对于一些测试的化合物，在所使用的生物测定中发现了活性的显著差异，这表明不同的识别系统可能起作用，并表明可以用特定的化合物来调节特定的细胞分裂素依赖性过程。证实了苯环上不同取代基的位置特异性空间效应和疏水效应对生物活性的影响。与其在生物测定中的高活性相反，在拟南芥AHK 3和AHK 4受体测定中，BAP衍生物的识别灵敏度比反式玉米素低得多。还研究了这些化合物对细胞周期蛋白依赖性激酶2（CDK 2）的作用以及对癌症和正常细胞系的抗增殖特性。几个测试的化合物显示出比BAP更强的抑制活性和细胞毒性。对人和植物CDKs的抑制作用分别与癌细胞和细胞分裂素依赖的烟草细胞的细胞增殖显著正相关。这表明，新的细胞分裂素的抗增殖作用的至少一部分是由于抑制CDK活性。(c)2005爱思唯尔有限公司保留所有权利。
To study the structure-activity relationships of aromatic cytokinins, the cytokinin activity at both the receptor and cellular levels, as well as CDK inhibitory and anticancer properties of 38 6-benzylaminopurine (BAP) derivatives were compared in various in vitro assays. The compounds were prepared by the condensation of 6-chloropurine with corresponding substituted benzylamines. The majority of synthesised derivatives exhibited high activity in all three of the cytokinin bioassays employed (tobacco callus, wheat senescence and Amaranthus bioassay). The highest activities were obtained in the senescence bioassay. For some compounds tested, significant differences of activity were found in the bioassays used, indicating that diverse recognition systems may operate and suggesting that it may be possible to modulate particular cytokinin-dependent processes with specific compounds. Position-specific steric and hydrophobic effects of different phenyl ring substituents on the variation of biological activity were confirmed. In contrast to their high activity in bioassays, the BAP derivatives were recognised with much lower sensitivity than trans-zeatin in both Arabidopsis thaliana AHK3 and AHK4 receptor assays. The compounds were also investigated for their effects on cyclin-dependent kinase 2 (CDK2) and for antiproliferative properties on cancer and normal cell lines. Several of the tested compounds showed stronger inhibitory activity and cytotoxicity than BAP. There was also a significant positive correlation of the inhibitory effects on human and plant CDKs with cell proliferation of cancer and cytokinin-dependent tobacco cells, respectively. This suggests that at least a part of the antiproliferative effect of the new cytokinins was due to the inhibition of CDK activity. (c) 2005 Elsevier Ltd. All rights reserved.