Abstract Cancer is one of the most common causes of death in modern medicine. Molecular design of novel substances with pharmacological activity is one of the goals of medicinal inorganic chemistry. Platinum complexes are widely used in the treatment of cancer, despite high efficacy their use is limited by side effects, as well as primary or acquired resistance. In this regard, the search for novel metal-containing antitumor compounds is underway. Organotins and gold compounds are promising pharmacological agents with anti-cancer properties. The introduction of protective antioxidant fragments into inorganic compounds molecules is a way to reduce the side effects of anti-cancer drugs on healthy cells. 2,6-dialkylphenols belonging to vitamin E (α-tocopherol) mimetics are widely used as antioxidants and stabilizers. The properties of Ph3SnCl (Sn-I), Ph3PAuCl (Au-I) and complexes Ph3SnSR (Sn-II) and Ph3PAuSR (Au-II) based on 2,6-di-tert-butyl-4-mercaptophenol (RSH) as radical scavengers and reducing agents were studied in model reactions. For Sn-II and Au-II the comparative study of cytotoxic action was made and the IC50 values on different cancer cell lines were found to be depended on the nature of metal. In general, Sn(IV) complexes possessed higher cytotoxicity than Au(I) complexes. In order to clarify the mechanism of cytotoxic mode of action the effect of compounds on Fe3+-induced lipid peroxidation, mitochondrial potential and mitochondrial permeability, cell cycle and induction of apoptosis was studied. Organotin compounds can bind tubulin SH-groups and inhibit its polymerization by a dose-dependent mechanism, whereas gold compounds inhibit Thioredoxin reductase (TrxR). In vivo experiments on acute toxicity of Sn-II and Au-II proved their moderate toxic action that opens prospects for the further study as antitumor agents.

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基于 Sn 和 Au 配合物的新型选择性抗癌剂。迷你评论

摘要 癌症是现代医学中最常见的死亡原因之一。具有药理活性的新型物质的分子设计是药物无机化学的目标之一。铂络合物广泛用于治疗癌症，尽管其疗效高，但其使用受到副作用以及原发性或获得性耐药性的限制。在这方面，正在寻找新型含金属的抗肿瘤化合物。有机锡和金化合物是具有抗癌特性的有前途的药剂。将保护性抗氧化剂片段引入无机化合物分子中是一种减少抗癌药物对健康细胞副作用的方法。属于维生素 E（α-生育酚）模拟物的 2,6-二烷基酚被广泛用作抗氧化剂和稳定剂。Ph3SnCl (Sn-I) 的性质，在模型反应中研究了基于 2,6-二叔丁基-4-巯基苯酚 (RSH) 作为自由基清除剂和还原剂的 Ph3PAuCl (Au-I) 和配合物 Ph3SnSR (Sn-II) 和 Ph3PAuSR (Au-II) . 对于 Sn-II 和 Au-II，进行了细胞毒性作用的比较研究，发现对不同癌细胞系的 IC50 值取决于金属的性质。一般来说，Sn(IV) 配合物比 Au(I) 配合物具有更高的细胞毒性。为了阐明细胞毒性作用模式的机制，研究了化合物对 Fe3+ 诱导的脂质过氧化、线粒体电位和线粒体通透性、细胞周期和诱导细胞凋亡的影响。有机锡化合物可以结合微管蛋白 SH 基团并通过剂量依赖性机制抑制其聚合，而金化合物则抑制硫氧还蛋白还原酶 (TrxR)。