Synthesis, anti-proliferative activity, and toxicity of C4(C5) substituted N,N′-bis(arylmethyl)imidazolium salts
Synthesis, anti-proliferative activity, and toxicity of C4(C5) substituted N,N′-bis(arylmethyl)imidazolium salts
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DOI：
10.1016/j.tet.2016.07.068
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发表时间：
2016-09-22
期刊：
影响因子：
2.1
通讯作者：
Youngs, Wiley J.
中科院分区：
文献类型：
--
作者：
Shelton, Kerri L.;DeBord, Michael A.;Youngs, Wiley J.
报道了咪唑环上带有亲水性或亲脂性取代基的C-4和C-5取代的N，N ′-双（芳甲基）咪唑盐的合成与表征。一项结构-活性关系研究表明，C-4和C-5位基团的亲脂性在调节对所测试的选定非小细胞肺癌细胞系的功效方面起着至关重要的作用。化合物11-17被确定为对所研究的细胞系组最有活性。化合物11和12由国家癌症研究所的发育治疗计划（Developmental Therapeutic Program）检测，其中在一剂量和五剂量测定中针对NCI-60人癌细胞系组测试它们。化合物11对测试的9种肺癌细胞系具有高活性，而12对60种细胞系中的59种具有细胞毒性作用。还在小鼠模型中研究了化合物11以确定其体内毒性。(C)2016由Elsevier Ltd.出版
The syntheses and characterization of C-4 and C-5 substituted N,N'-bis(arylmethyl)imidazolium salts with hydrophilic or lipophilic substituents on the imidazole ring are reported. A structure-activity relationship study revealed that the lipophilicity of groups at the C-4 and C-5 positions plays a crucial role in modulating the efficacy against select non-small cell lung cancer cell lines tested. Compounds 11-17 were determined to be the most active against the panel of cell lines studied. Compounds 11 and 12 were examined by the National Cancer Institute's Developmental Therapeutic Program where they were tested against the NCI-60 human cancer cell line panel in a one-dose and five-dose assay. Compound 11 had high activity against the nine lung cancer lines tested while 12 had cytotoxic effects against 59 of the 60 cell lines. Compound 11 was also studied in a murine model to determine its in vivo toxicity. (C) 2016 Published by Elsevier Ltd.