一种金属环铱配合物作为 c-myc G-四链体稳定剂和下调 c-myc 癌基因表达的调节剂。

A cyclometallated iridium(III) complex as a c-myc G-quadruplex stabilizer and down-regulator of c-myc oncogene expression.

机构信息

Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.

出版信息

Curr Med Chem. 2013;20(4):576-82. doi: 10.2174/0929867311320040009.

DOI:10.2174/0929867311320040009

Abstract

A new cyclometallated iridium(III) complex with the 2,2'-biquinoline N-donor ligand has been synthesized and characterized. The interaction and affinity of the complex towards c-myc G-quadruplex and duplex DNA have been investigated using UV/Vis spectroscopy and gel mobility shift assay. These studies revealed that complex 1 binds to c-myc G-quadruplexes (Pu22 and Pu27) with high affinity but does not interact with duplex DNA either by intercalation or groove binding. The ability of 1 to stabilize c-myc G-quadruplex DNA in vitro has also been examined through a PCR stop assay and a cell-based luciferase reporter assay. Complex 1 displays promising cytotoxic activity against the HeLa cell line with sub-micromolar potency.

摘要

合成并表征了一种具有 2,2'-联喹啉 N-供体配体的新型环金属铱（III）配合物。使用紫外/可见光谱法和凝胶迁移率变动分析研究了配合物 1 与 c-myc G-四链体和双链 DNA 的相互作用和亲和力。这些研究表明，配合物 1 与 c-myc G-四链体（Pu22 和 Pu27）具有高亲和力，但既不通过嵌入也不通过沟结合与双链 DNA 相互作用。还通过 PCR 停止测定法和基于细胞的荧光素酶报告基因测定法检查了 1 稳定体外 c-myc G-四链体 DNA 的能力。配合物 1 对 HeLa 细胞系表现出有希望的细胞毒性活性，其效力低于亚微摩尔。