N-哌嗪烷基酰胺类化合物的合成与DNA相互作用及生理活性

为研究多胺类化合物的抗肿瘤活性, 合成了9个哌嗪烷基酰胺衍生物, 其结构经¹H NMR, MS及元素分析确证. 合成的化合物与三个作为酰化剂的消炎药物萘普生、布洛芬和联苯乙酸及抗癌药物五氟尿嘧啶一并对人口腔上皮癌细胞(KB)、人肺癌细胞(A-549)、乳腺癌细胞(MDA)、人肝癌细胞(Bel-7402)四种肿瘤细胞进行了体外抑制率测试. 结果表明, 所合成的化合物对KB细胞和Bel-7402细胞有正抑制作用, 但对A-549和MDA细胞呈负抑制作用, 意外的是四种商品药物也有类似结果. 还测试了对酪氨酸激酶的抑制作用, 未发现明显活性. 联苯乙酸和N-2-哌嗪基-乙基-4-联苯乙酰胺对DNA荧光光谱的影响表明联苯乙酸可嵌入DNA而后者没有表现出多胺衍生物与DNA的嵌入式作用.

Synthesis, Interaction with DNA and Bioactivity of N-Piperazinoalkylamide

Nine novel N-piperazinoalkylamide derivatives were synthesized and their structures were con- firmed by 1H NMR, MS spectra and elemental analysis. All the target compounds, together with the four commercial drugs, naproxen, 4-biphenylacetic acid, brufen (as the acyl agents) and 5-fluorouracil, were tested in vitro for their inhibition on four kinds of human cancer cells, KB, A-549, MDA and Bel-7402. The data showed that all the synthesized compounds exhibited positive effect on KB and Bel-7402 cells, but negative effect on A-549 and MDA cells, while the commercial medicines had the similar results unexpect- edly. In addition, the inhibition rate of 4-biphenylacetic acid and naproxen on Bel-7402 cell was equivalent with 5-fluorouracil, while their inhibition on KB cell was higher than that of 5-fluorouracil. The inhibitory ability of the samples on tyrosine kinase was also measured, however no obvious effect was found. The fluorescence spectra of 13a and 4-biphenylacetic acid demonstrated that 13a did not show the interaction with DNA while 4-biphenylacetic acid exhibited the intercalary effect on DNA.