PDF(Pubmed)
Abstract：
Copper-organic compounds have gained momentum as potent antitumor drug candidates largely due to their ability to generate an oxidative burst upon the transition of Cu2+ to Cu1+ triggered by the exogenous-reducing agents. We have reported the differential potencies of a series of Cu(II)-organic complexes that produce reactive oxygen species (ROS) and cell death after incubation with N-acetylcysteine (NAC). To get insight into the structural prerequisites for optimization of the organic ligands, we herein investigated the electrochemical properties and the cytotoxicity of Cu(II) complexes with pyridylmethylenethiohydantoins, pyridylbenzothiazole, pyridylbenzimidazole, thiosemicarbazones and porphyrins. We demonstrate that the ability of the complexes to kill cells in combination with NAC is determined by the potential of the Cu+2 → Cu+1 redox transition rather than by the spatial structure of the organic ligand. For cell sensitization to the copper-organic complex, the electrochemical potential of the metal reduction should be lower than the oxidation potential of the reducing agent. Generally, the structural optimization of copper-organic complexes for combinations with the reducing agents should include uncharged organic ligands that carry hard electronegative inorganic moieties.
摘要：
铜有机化合物作为有效的抗肿瘤药物候选物获得了势头，这主要是由于它们能够在外源性还原剂触发的Cu2向Cu1转变时产生氧化爆发。我们已经报道了与N-乙酰半胱氨酸（NAC）孵育后产生活性氧（ROS）和细胞死亡的一系列Cu（II）-有机复合物的不同效力。为了深入了解有机配体优化的结构先决条件，我们在此研究了Cu（II）与吡啶基亚甲基硫因的配合物的电化学性质和细胞毒性，吡啶基苯并噻唑，吡啶基苯并咪唑，氨基硫脲和卟啉。我们证明，配合物与NAC结合杀死细胞的能力取决于Cu2→Cu1氧化还原转变的潜力，而不是有机配体的空间结构。为了使细胞对铜有机络合物敏感，金属还原的电化学电位应低于还原剂的氧化电位。一般来说,与还原剂组合的铜-有机络合物的结构优化应包括携带硬电负性无机部分的不带电荷的有机配体。
