Copper-based binuclear enantiomeric complexes 1_S and 1_R were synthesized as anticancer chemotherapeutic agents to target G-quadruplex rich region of DNA and thoroughly characterized by various spectroscopic and single X-ray crystal diffraction studies. The structure elucidation of Schiff base ligand L_S and complexes 1_S & 1_R, was carried out by single crystal X-ray studies which showed that ligand crystallized in the monoclinic P21/n space group while complexes 1_S and 1_R crystallized in triclinic space groups P and P1, respectively with two copper units connected to each other via an alkoxide bridge to exhibit square planar geometry which is in good agreement with other spectroscopic studies {IR, ESI-MS, EPR and magnetic moment values}. In vitro binding studies of complexes 1_S and 1_R were carried out with G-quadruplex DNA and CT-DNA which showed higher binding affinity and selectivity toward quadruplex DNA over the duplex DNA. To validate the potential of complexes to act as therapeutic drug candidates, the cleavage studies of complexes 1_S and 1_R were carried out with G-quadruplex telomeric DNA by PAGE Gel assay which showed sequence selective cleavage of 22G4via oxidative cleavage pathway. The major cleavage sites identified were G15, T6, G8, G9, G14 for complex 1_S whereas for 1_R G15, G20, G21, G14 cleavage sites were observed. Furthermore, these complexes were capable of cleaving pUC19 plasmid DNA in double-stranded non-random fashion which is considered to be more potent than single-strand cleavage as a source of lethal DNA lesions. Cellular studies of 1_S and 1_R were performed on a panel of human cancer cell lines; Huh7, MCF7, BxPC3 and AsPC1, which displayed significant cytotoxicity and differential responses toward different cancer phenotypes.

中文翻译：

---

对映体铜基抗癌剂促进 G-四链体端粒 DNA 的序列选择性切割和质粒 DNA 的非随机切割。

铜基双核对映体复合物1 _S和1 _R被合成为抗癌化学治疗剂，以靶向 DNA 的富含 G-四链体的区域，并通过各种光谱和单 X 射线晶体衍射研究彻底表征。席夫碱配体L _S和配合物1 _S & 1 _R的结构解析是通过单晶 X 射线研究进行的，结果表明配体在单斜P 21/ n空间群中结晶，而配合物1 _S和1 _R在单斜P 21/ n空间群中结晶。三斜空间群P和P 1 分别具有通过醇盐桥相互连接的两个铜单元，以呈现方形平面几何形状，这与其他光谱研究{IR、ESI-MS、EPR 和磁矩值}非常一致。复合物1 _S和1 _{R 的}体外结合研究是用 G-四链体 DNA 和 CT-DNA 进行的，其对四链体 DNA 的结合亲和力和选择性高于双链体 DNA。为了验证复合物作为治疗药物候选物的潜力，复合物1 _S和1 _R的裂解研究用 G-四链体端粒 DNA 通过 PAGE 凝胶测定进行，显示通过氧化裂解途径对 22G4进行序列选择性裂解。确定的主要切割位点是复合物1 _{S 的}G15、T6、G8、G9、G14，而对于1 _R，观察到 G15、G20、G21、G14 切割位点。此外，这些复合物能够以双链非随机方式切割 pUC19 质粒 DNA，这被认为比单链切割更有效，作为致死 DNA 损伤的来源。1 _S和1 _{R 的}细胞研究在一组人类癌细胞系上进行；Huh7、MCF7、BxPC3 和 AsPC1，它们对不同的癌症表型显示出显着的细胞毒性和不同的反应。