Mahendiran Dharmasivam, Kumar Raju Senthil, Viswanathan Vijayan, Velmurugan Devadasan, Rahiman Aziz Kalilur
Post-Graduate and Research Department of Chemistry, The New College (Autonomous), Chennai, 600 014, India.
Department of Pharmaceutical Chemistry, Swamy Vivekanandha College of Pharmacy, Elayampalayam, Tiruchengodu, 637 205, India.
J Biol Inorg Chem. 2017 Oct;22(7):1109-1122. doi: 10.1007/s00775-017-1488-6. Epub 2017 Sep 7.
The bis(4'-(4-tolyl)-2,2':6',2″-terpyridine)copper(II) complex [Cu(ttpy)]Cl was synthesized and authenticated by single crystal analysis, which shows distorted octahedral geometry around copper(II) ion. The crystal packing is stabilized by C-H···π inter and intramolecular interactions. The complex was found to be lipophilic as determined by shake-flask method. In vitro cytotoxicity of the complex was tested against Ehrlich ascites carcinoma (EAC) and L6 myotube cell lines. The complex exhibit potent cytotoxicity with respect to the commercially available anticancer drug cisplatin. Hoechst 33258, AO/EB and PI (flow cytometry) staining methods suggest that the complex can induce apoptosis in EAC cells. Cell cycle analyses also support the induced apoptosis. Cellular uptake studies revealed that the complex can go into the cytoplasm and accumulate in the cell nuclei. The complex induces EAC cell apoptosis through a ROS-mediated mitochondrial pathway by activating caspase 3 and caspase 7 and regulates the Bcl-2 family proteins. In vivo study of the complex was validated against the animal tumor growth (EAC) cell in Swiss albino mice. The bis(4'-(4-tolyl)-2,2':6',2″-terpyridine)copper(II) complex induces EAC cell apoptosis through a ROS-mediated mitochondrial pathway and significantly reduced the body weight and solid tumor volume in Swiss albino mice.
合成了双（4'-（4-甲苯基）-2,2':6',2″-三联吡啶）铜（II）配合物[Cu(ttpy)]Cl，并通过单晶分析进行了鉴定，该分析表明铜（II）离子周围具有扭曲的八面体几何结构。晶体堆积通过C-H···π分子间和分子内相互作用得以稳定。通过摇瓶法测定发现该配合物具有亲脂性。测试了该配合物对艾氏腹水癌（EAC）和L6肌管细胞系的体外细胞毒性。相对于市售抗癌药物顺铂，该配合物表现出强大的细胞毒性。Hoechst 33258、AO/EB和PI（流式细胞术）染色方法表明该配合物可诱导EAC细胞凋亡。细胞周期分析也支持诱导凋亡。细胞摄取研究表明该配合物可进入细胞质并在细胞核中积累。该配合物通过激活半胱天冬酶3和半胱天冬酶7，通过ROS介导的线粒体途径诱导EAC细胞凋亡，并调节Bcl-2家族蛋白。在瑞士白化小鼠中针对动物肿瘤生长（EAC）细胞对该配合物进行了体内研究验证。双（4'-（4-甲苯基）-2,2':6',2″-三联吡啶）铜（II）配合物通过ROS介导的线粒体途径诱导EAC细胞凋亡，并显著降低了瑞士白化小鼠的体重和实体瘤体积。
