Novel DNA bis-intercalators of isoquinolino[4,5-bc]acridines:: design, synthesis and evaluation of cytotoxic activity
Novel DNA bis-intercalators of isoquinolino[4,5-bc]acridines:: design, synthesis and evaluation of cytotoxic activity
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DOI：
10.1016/j.tet.2005.09.065
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发表时间：
2005-12-12
期刊：
影响因子：
2.1
通讯作者：
Qian, XH
中科院分区：
文献类型：
--
作者：
Yang, P;Yang, Q;Qian, XH
设计并合成了单、双核异喹啉并[4，5-bc]吖啶衍生物，并对其DNA结合活性和细胞毒活性进行了评价。A4诱导超螺旋质粒pBR 322 DNA解旋（36 ± 2）度，A6诱导解旋（41 ± 1）度，均高于单类似物A1（19 ± 2）度。A6对人肺癌细胞A549的体外抗肿瘤活性最高，A4对小鼠白血病细胞P388的体外抗肿瘤活性最高。DNA结合常数和分子模型表明，连接链的长度和发色团间的距离是影响DNA结合亲和力和生物活性的关键因素。(c)2005爱思唯尔有限公司保留所有权利。
Mono- and dinuclear isoquinolino[4,5-bc]acridine derivatives were designed and facilely synthesized, their DNA-binding affinities and cytotoxic activities were evaluated. A4 induced unwinding of supercoiled plasmid pBR 322 DNA by (36 +/- 2)degrees while A6 induced that by (41 +/- 1)degrees, both of which were higher than the mono-analogue A1 ((19 +/- 2)degrees). A6 exhibited the highest in vitro antitumor, activity against human lung cancer cell (A549) and A4 was the most active one against murine leukemia cell (P388). DNA binding constant and molecular model indicated that both the length of linker chain and the distance of interchromophore were key impact factors for DNA binding affinity and biological activity. (c) 2005 Elsevier Ltd. All rights reserved.