Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore, 632014, India.
ChemMedChem. 2023 Apr 17;18(8):e202200652. doi: 10.1002/cmdc.202200652. Epub 2023 Mar 6.
Cancer is a deadly disease associated with abnormal cell growth and invasion to various parts of the body. Many drugs such as cisplatin and carboplatin have been used for the treatment of cancer over the years. However, a lack of selectivity toward cancer cells and associated side effects with current treatment options has fueled continued efforts throughout the world to find better anticancer drugs. Over the past decades, copper-containing compounds have shown excellent anticancer activity. Cu(II) complexes are well studied and show broad-spectrum pharmacological activity. The redox activity of copper ions contributes to cytotoxic activity in combination with ligands that possess bioactivity. Binding of copper with various types of bidentate, tridentate, and tetradentate ligands can activate the processes of necrosis, apoptosis, and angiogenesis. Copper induces the formation of reactive oxygen species to cleave DNA. Similarly, light-assisted excitation of Cu(II) complexes in the red region of the electromagnetic spectrum helps produce different reactive species, thereby inducing anticancer activity through a photodynamic mechanism. In general, in vivo and in vitro studies have demonstrated that the administration of copper ions is effective against various cancer cell lines. Herein we discuss the past ten years of research into copper complexes of terpyridine-, 2,2'-bipyridine-, and 1,10-phenanthroline-based ligands as potential anticancer agents. The aspects of chemotherapy by redox-mediated pathways and photodynamic therapy using light-assisted excitation are reviewed, with a focus on mechanisms of activity, details of important experimental procedures, as well as drawbacks in the design of copper-containing drugs.
癌症是一种与异常细胞生长和侵袭身体各部位相关的致命疾病。多年来,顺铂和卡铂等许多药物已被用于癌症治疗。然而,由于目前的治疗方案缺乏对癌细胞的选择性以及相关的副作用,世界各地仍在继续努力寻找更好的抗癌药物。在过去的几十年中,含铜化合物已显示出优异的抗癌活性。Cu(II)配合物已得到广泛研究,具有广谱的药理活性。铜离子的氧化还原活性与具有生物活性的配体结合,导致细胞毒性活性。铜与各种类型的双齿、三齿和四齿配体结合可以激活坏死、凋亡和血管生成过程。铜诱导活性氧的形成以切割 DNA。同样,在电磁光谱的红色区域用光辅助激发 Cu(II)配合物有助于产生不同的活性物质,从而通过光动力机制诱导抗癌活性。一般来说,体内和体外研究表明,铜离子的给药对各种癌细胞系有效。本文讨论了过去十年中基于三联吡啶、2,2'-联吡啶和 1,10-菲咯啉的配体的铜配合物作为潜在抗癌剂的研究。综述了通过氧化还原介导途径进行化疗和用光辅助激发进行光动力疗法的方面,重点介绍了活性机制、重要实验程序的细节以及含铜药物设计中的缺陷。