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.
A novel polydentate chelating antioxidant ligand and series of organotin complexes on its base were synthesized and characterized by NMR 1H, 13C, 119Sn, IR spectroscopy, X-ray, and elemental analysis. Their antioxidant activity was evaluated in DPPH and NBT-tests, and as lipoxygenase inhibitory activity. It was shown that ligand alone is a radical scavenger, while introducing tin in the structure of the compound significantly decreases its activity. For the ligand alone the ability to strongly suppress the formation of advanced glycation end products (AGEs) was shown, which may be associated with the established antiradical activity. All synthesized compounds appeared to be moderate lipoxygenase inhibitors. The stability of compounds to hydrolysis under different pH was estimated. The ligand undergoes decomposition after about an hour, while organotin complexes on its base demonstrate vast stability, showing signs of decomposition only after 5 h of experimentation. Cytotoxicity of compounds was studied by standard MTT-test, which showed unorthodox results: the ligand itself demonstrated noticeable cytotoxicity while the introduction of organotin moiety either did not affect the toxicity levels or reduced them instead of increasing. Organotin complexes possess luminescence both as powders and DMSO solutions, its quantum yields reaching 67% in DMSO. The combination of luminescence with unique cytotoxic properties allows us to propose the synthesized compounds as perspective theranostic agents.
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