Novel selective anticancer agents based on Sn and Au complexes. Mini-reviewстатья
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Дата последнего поиска статьи во внешних источниках: 30 сентября 2020 г.
Аннотация: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.