Du Jun, Zhang Erlong, Zhao Yao, Zheng Wei, Zhang Yang, Lin Yu, Wang Zhaoying, Luo Qun, Wu Kui, Wang Fuyi
College of Chemistry and Materials Science, Key Laboratory of Functional Molecular Solids, The Ministry of Education, Anhui Laboratory of Molecular-Based Materials, Anhui Normal University, Wuhu 241000, P. R. China.
College of Chemistry and Materials Science, Key Laboratory of Functional Molecular Solids, The Ministry of Education, Anhui Laboratory of Molecular-Based Materials, Anhui Normal University, Wuhu 241000, P. R. China and Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Beijing Centre for Mass Spectrometry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.
Metallomics. 2015 Dec;7(12):1573-83. doi: 10.1039/c5mt00122f.
Ruthenium based complexes are promising antitumour candidates due to their lower toxicity and better water-solubility compared to the platinum antitumour complexes. An epidermal growth factor receptor (EGFR) has been found to be overexpressed in a large set of tumour cells. In this work, a series of organoruthenium complexes containing EGFR-inhibiting 4-anilinoquinazoline pharmacophores were synthesised and characterised. These complexes exhibited excellent inhibitory activity against EGFR and high affinity to interact with DNA via minor groove binding, featuring dual-targeting properties. In vitro screening demonstrated that the as-prepared ruthenium complexes are anti-proliferating towards a series of cancer cell lines, in particular the non-small-cell lung cancer cell line A549. Fluorescence-activated cell sorting analysis and fluorescence microscopy revealed that the most active complex 3 induced much more early-stage cell apoptosis than its cytotoxic arene ruthenium analogue and the EGFR-inhibiting 4-anilinoquinazolines, verifying the synergetic effect of the two mono-functional pharmacophores.
与铂类抗肿瘤配合物相比，钌基配合物因其较低的毒性和更好的水溶性而成为有前景的抗肿瘤候选物。已发现表皮生长因子受体（EGFR）在大量肿瘤细胞中过表达。在这项工作中，合成并表征了一系列含有抑制EGFR的4-苯胺基喹唑啉药效基团的有机钌配合物。这些配合物对EGFR表现出优异的抑制活性，并通过小沟结合与DNA相互作用具有高亲和力，具有双靶向特性。体外筛选表明，所制备的钌配合物对一系列癌细胞系具有抗增殖作用，特别是对非小细胞肺癌细胞系A549。荧光激活细胞分选分析和荧光显微镜显示，活性最高的配合物3比其细胞毒性芳烃钌类似物和抑制EGFR的4-苯胺基喹唑啉诱导更多的早期细胞凋亡，证实了两种单功能药效基团的协同作用。
