Antitumour indolequinones: synthesis and activity against human pancreatic cancer cells.
Antitumour indolequinones: synthesis and activity against human pancreatic cancer cells.
复制标题
DOI：
10.1039/c4ob00711e
复制
发表时间：
2014-07-21
影响因子：
3.2
通讯作者：
Moody CJ
中科院分区：
文献类型：
--
作者：
Inman M;Visconti A;Yan C;Siegel D;Ross D;Moody CJ
吲哚醌对胰腺癌细胞的生长抑制活性的一个重要决定因素是在2-位上被2-未取代的衍生物取代，其明显更有效。一系列的吲哚醌轴承的范围内的氮上的取代基，并在吲哚基carbinyl的位置制备由铜（II）介导的溴醌和烯胺的反应，然后通过官能团相互转化。然后测定化合物抑制胰腺癌细胞生长的能力。在3-位的离去基团的pKa显示影响生长抑制活性，这与所提出的还原、离去基团的损失和反应性亚胺物质的形成的作用机制一致。吲哚氮上的取代耐受性良好，对生长抑制活性的影响不大，而在5-和6-位取代大于甲氧基导致活性降低。提出的研究定义了最佳生长抑制活性所需的2-未取代的吲哚醌的取代范围。
An important determinant of the growth inhibitory activity of indolequinones against pancreatic cancer cells is substitution on the 2-position with 2-unsubstituted derivatives being markedly more potent. A series of indolequinones bearing a range of substituents on nitrogen and at the indolylcarbinyl position was prepared by copper(II)-mediated reaction of bromoquinones and enamines, followed by functional group interconversions. The compounds were then assayed for their ability to inhibit the growth of pancreatic cancer cells. The pKa of the leaving group at the 3-position was shown to influence growth inhibitory activity that is consistent with the proposed mechanism of action of reduction, loss of leaving group and formation of a reactive iminium species. Substitutions on the indole nitrogen were well tolerated with little influence on growth inhibitory activity while substitutions at the 5- and 6- positions larger than methoxy led to decreased activity. The studies presented define the range of substitutions of 2-unsubstituted indolequinones required for optimal growth inhibitory activity.
登录
查看更多内容
影响因子：
7.3
作者：
Naylor, MA;Jaffar, M;Stratford, IJ
通讯作者：
Stratford, IJ
影响因子：
5.2
作者：
Huang, Baohua;Desai, Ankur;Tang, Shengzhuang;Thomas, Thommey P.;Baker, James R., Jr.
通讯作者：
Baker, James R., Jr.
影响因子：
2.8
作者：
Inman, Martyn;Moody, Christopher J.
通讯作者：
Moody, Christopher J.
影响因子：
2.7
作者：
Huang, Baohua;Tang, Shengzhuang;Baker, James R., Jr.
通讯作者：
Baker, James R., Jr.
DOI：
10.1039/b009652k
发表时间：
2001-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2
影响因子：
--
作者：
Everett, SA;Naylor, MA;Moody, CJ
通讯作者：
Moody, CJ