title: Discovery of a dual-targeting organometallic ruthenium complex with high activity inducing early stage apoptosis of cancer cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.affiliation: 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. fuyi.wang@iccas.ac.cn yaozhao@iccas.ac.cn.
authors.forename: Erlong
authors.initials: E
authors.lastname: Zhang
authors.affiliation: 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. fuyi.wang@iccas.ac.cn yaozhao@iccas.ac.cn.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: 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. fuyi.wang@iccas.ac.cn yaozhao@iccas.ac.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: 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. fuyi.wang@iccas.ac.cn yaozhao@iccas.ac.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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. fuyi.wang@iccas.ac.cn yaozhao@iccas.ac.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lin
authors.affiliation: 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. fuyi.wang@iccas.ac.cn yaozhao@iccas.ac.cn.
authors.forename: Zhaoying
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 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. fuyi.wang@iccas.ac.cn yaozhao@iccas.ac.cn.
authors.forename: Qun
authors.initials: Q
authors.lastname: Luo
authors.affiliation: 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. fuyi.wang@iccas.ac.cn yaozhao@iccas.ac.cn.
authors.forename: Kui
authors.initials: K
authors.lastname: Wu
authors.affiliation: 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. fuyi.wang@iccas.ac.cn yaozhao@iccas.ac.cn.
authors.forename: Fuyi
authors.initials: F
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D006801:Humans; D006868:Hydrolysis; D062105:Molecular Docking Simulation; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology; D011799:Quinazolines; D012428:Ruthenium / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D011799:Quinazolines; D012428:Ruthenium