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, Swami Vivekanandha College of Pharmacy, Elayampalayam, Tiruchengodu 637 205, India.
Dalton Trans. 2016 May 4;45(18):7794-814. doi: 10.1039/c5dt03831f.
A series of homoleptic bis(terpyridine)copper(ii) complexes of the type [Cu(L(1-5))2]Cl2 (), where L(1-5) = 4'-(4-substituted)-2,2':6',2''-terpyridines, have been synthesized and characterized. The molecular structure of complex was confirmed by the single crystal XRD technique, and the geometry of the complexes is best described as distorted octahedral. Structural parameters from the crystallographic and DFT studies are in good agreement with each other. The small HOMO-LUMO energy gap supports bioefficacy of the complexes. DNA binding studies show high intrinsic binding constant values 1.53 ± 0.15, 1.62 ± 0.08 and 3.09 ± 0.12 × 10(5) M(-1) for complexes , and , respectively, with intercalative mode of binding to CT-DNA. The binding results were further supported by molecular docking studies. The experimental results indicate that the interaction between the complexes and BSA protein involves a static quenching mechanism. The molecular docking studies with c-Met tyrosine kinase receptors show hydrophobic and π-π interactions. All the complexes bring about hydroxyl radical mediated DNA cleavage in the presence of H2O2. In vitro cytotoxicities of the complexes () were tested against three cancerous cell lines, namely human breast adenocarcinoma (MCF-7), epithelioma (Hep-2) and cervical (HeLa) cell lines, and one non-tumorigenic human dermal fibroblast (NHDF) cell line by MTT reduction assay. The morphological assessment data obtained using Hoechst 33258 staining revealed that complex induces apoptosis much more effectively than the other complexes.
已合成并表征了一系列通式为[Cu(L(1 - 5))2]Cl2（）的同配双（三联吡啶）铜（II）配合物，其中L(1 - 5) = 4'-(4-取代基)-2,2':6',2''-三联吡啶。通过单晶XRD技术确定了配合物的分子结构，配合物的几何构型最好描述为扭曲八面体。晶体学和DFT研究得到的结构参数彼此吻合良好。较小的HOMO-LUMO能隙支持了配合物的生物活性。DNA结合研究表明，配合物、和与CT-DNA的结合模式为插入式，其固有结合常数分别为1.53 ± 0.15、1.62 ± 0.08和3.09 ± 0.12 × 10(5) M(-1)。分子对接研究进一步支持了结合结果。实验结果表明，配合物与BSA蛋白之间的相互作用涉及静态猝灭机制。与c-Met酪氨酸激酶受体的分子对接研究显示存在疏水和π-π相互作用。所有配合物在H2O2存在下均能引发羟基自由基介导的DNA裂解。通过MTT还原试验测试了配合物（）对三种癌细胞系，即人乳腺腺癌（MCF-7）、上皮瘤（Hep-2）和宫颈（HeLa）细胞系，以及一种非致瘤性人皮肤成纤维细胞（NHDF）细胞系的体外细胞毒性。使用Hoechst 33258染色获得的形态学评估数据表明，该配合物比其他配合物更有效地诱导细胞凋亡。
