Inhibition of Horse Liver Alcohol Dehydrogenase by Methyltin Compounds

The study of inorganic tin (SnCl2, SnCl4) and methyltin compounds (MeSnCl3, Me2SnCI2, Me3SnCl) effects on the enzymatic activity of alcohol dehydrogenase (ADH) in the reaction of ethanol oxidation has been carried out. The experimental results of the study show that inorganic tin and methyltin substances induce slight inhibition of the catalytic activity of horse liver alcohol dehydrogenase (HLADH), unable to be improved during pre-incubation with the enzyme. The conditions for carrying out the kinetic investigation of the mentioned phenomenon were optimized and as it turned out the mechanism of methyltin trichloride action, as the most effective methyltin inhibitor, is more complex than the proposed interaction of the metal atom with SH-groups of the enzyme protein. It was demonstrated that the tin compounds act in the same manner as methylmercury compounds and might serve as oxidative agents towards the co-enzyme NADH. Kinetic data on MeSnCl3 were calculated. Data acquired on NAD-dependent ADH from horse liver and those regarding NAD-dependent LDH from sturgeon liver were compared

Inhibition of Horse Liver Alcohol Dehydrogenase by Methyltin Compounds

ABSTRACT The study of inorganic tin (SnCI2, SnCt4) and methyltin compou.nds (MeSnC13, Me2SnCI, Me3SnC1) effects on the enzymatic activity of alcohol dehydrogenase (ADH) in the reaction of ethanol oxidation has been carried out. The experimental results of the study show that inorganic tin and methyltin substances induce slight inhibition of the catalytic activity of horse liver alcohol dehydrogenase (HLADH), unable to be improved during pre-incubation with the enzyme. The conditions for carrying out the kinetic investigation of the mentioned phenomenon were optimized and as it turned out the mechanism of methyltin trichloride action, as the most effective methyltin inhibitor, is more complex than the proposed interaction of the metal atom with SH-groups of the enzyme protein. It was demonstrated that the tin compounds act in the same manner as methylmercury compounds and might serve as oxidative agents towards the co-enzyme NADH. Kinetic data on MeSnCI3 were calculated. Data acquired on NAD-dependent ADH from horse liver and those regarding NAD-dependent LDH from sturgeon liver were compared

Protective Effect of Meso-Tetrakis-(3,5-di-tert-butyl-4-hydroxyphenyl)porphyrin on the In Vivo Impact of Trimethyltin Chloride on the Antioxidative Defense System

The in vivo effect of trimethyltin chloride (Me(3)SnCl), free base meso-tetrakis(3,5-di-tert-butyl-4-hydroxyphenyl)porphyrin (R′(4)PH(2)) and their equimolar mixture, on the enzymatic activity of catalase (CAT), superoxide dismutase (SOD), and on the total content of free sulfhydryl groups has been studied in rat liver and kidney. It was demonstrated that the simultaneous treatment of tested animals with the combination of Me(3)SnCl and R′(4)PH(2) reduced the toxic impact of Me(3)SnCl

Impact of organotin compounds on the growth of epidermoid Lewis carcinoma

Search for new compounds with a broad antitumor and antimetastatic potency due to multiple targeting remains important in medicinal chemistry, pharmacology and oncology. We report the efficacy of hybrid organotin agents bis-(3,5-di-tert-butyl-4-hydroxyphenylthiolate) dimethyltin (Ме3) and (3,5-di-tert-butyl-4-hydroxyphenylthiolate) triphenyltin (Ме5

Evaluation of the pharmacological activity of hybrid organotin compounds in a B16 melanoma model in the classical and metronomic administration modes

In modern medical chemistry, much attention is paid to the search for new antimetastatic agents based on metal compounds. Organotin compounds promise to be good candidates as the treatment of malignant neoplasms. In order to reduce a possible nonspecific toxic effect of tin compounds and to expand the intended therapeutic use, the paper presents hybrid tin (IV) complexes with Sn-S bond containing a fragment of 2,6-di-tert-butylpheno

Protein ruthenation and DNA alkylation: chlorambucil-functionalized RAPTA complexes and their anticancer activity

Chemotherapeutics for the treatment of tumorigenic conditions that feature novel modes of action are highly sought after to overcome the limitations of current chemotherapies. Herein, we report the conjugation of the alkylating agent chlorambucil to the RAPTA scaffold, a well-established pharmacophore. While chlorambucil is known to alkylate DNA, the RAPTA complexes are known to coordinate to amino acid side chains of proteins. Therefore, such a molecule combines DNA and protein targeting properties in a single molecule. Several chlorambucil-tethered RAPTA derivatives were prepared and tested for their cytotoxicity, stability in water and reactivity to protein and DNA substrates. The anticancer activity of the complexes is widely driven by the cytotoxicity of the chlorambucil moiety. However, especially in the cis-platin-resistant A2780R cells, the chlorambucil-functionalized RAPTA derivatives are in general more cytotoxic than chlorambucil and also a mixture of chlorambucil and the parent organoruthenium RAPTA compound. In a proof-of-principle experiment, the cross-linking of DNA and protein fragments by a chlorambucil-RAPTA derivative was observed

Dichloro[<i>N</i>-[(η⁶-phenyl)methyl]-4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8tetrahydronaphthalen-2-yl)vinyl)benzamide](1,3,5-triaza-7-phosphatricyclo [3.3.1.1^3,7]decane-κP⁷)ruthenium

Bexarotene-tethered RuII(arene) compounds with 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (PTA) were prepared as an analog of RAPTA antitumor complexes in order to evaluate their in vitro antiproliferative activity against human cancer cell lines

Ruthenium(II)–arene and triruthenium-carbonyl cluster complexes with new water-soluble phopsphites based on glucose: Synthesis, characterization and antiproliferative activity

New water-soluble 3,5,6-bicyclophosphite ligands based on glucose modified with uracil, 5-fluorouracil or thymine are reported. The phosphite ligands were subsequently reacted with bis[dichlorido(η6-p-cymene)ruthenium(II)] and trirutheniumdodecacarbonyl to afford monoruthenium analogues of RAPTA-C and triruthenium clusters with 1–3 phosphite ligands, respectively. The influence of ligands on the stability of the compounds and the antiproliferative activity of the compounds was investigated