Thioamides as radical scavenging compounds: Methods for screening antioxidant activity and detection.

Heteroaromatic thiols and thiones attracted the attention of chemists, pharmacologists and biochemists because of participation in the interception of free radicals. For the first time offered independent and reliable methods for evaluating of the antioxidant activity of thioamides-derivatives of pyridine, quinoline, imidazole, triazole, tetrazole, pyrimidine, pyrrolidine and 7-mercapto-4-methylcoumarin -based on kinetic parameters of the thioamide reaction with chromogenic radical (rate constant, M(-1)min(-1) and time to decrease concentration of test free radical by 50%, TEC50, min) or thermodynamics of the thioamides reaction with molecular iodine (extent of thioamide conversion, %). To compare the antioxidant activity of thioamides and widely used standard-antioxidant Trolox (6-Hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid) we have proposed to use a value of relative antioxidant activity constant. As it was established, the kinetics of interaction between the chromogenic radical and thioamides in the presence of an excess of 2,2'-diphenyl-1-picrylhydrazyl (DPPH) is described by the kinetics of the pseudo first order with respect to the reacting components. A kinetic-spectrophotometric method for the quantification of heteroaromatic thioamides is elaborated and was tested in the analysis of urine. Thioamides were detected at concentrations of 1.53µgml(-1), RSD=4.6% (2-mercaptoimidazole, V), 2.08µgml(-1), RSD=1.8% (1-methylimidazoline-2-thione, VI), 1.45µgml(-1), RSD=4.3% (2-mercaptopyridine, IX).The proposed procedures show good precision and accuracy of the results obtained.

Formation of toxic metabolites from thiabendazole and other thiazoles in mice. Identification of thioamides as ring cleavage products.

The metabolism of three nephro- or hepatotoxic thiazoles--2-(thiazol-4-yl)benzimidazole (thiabendazole) (1a), 4-tert-butyl-2-methyl-thiazole (1b), and 2-(p-methoxyphenyl)-4-methylthiazole (1c)--was examined in mice with special regard to the formation of ring cleavage products. By GC/MS analyses of derivatized metabolites and comparison with authentic samples, thioformamide and benzimidazol-2-ylglyoxal as the accompanying fragment were identified as urinary metabolites in mice dosed with 1a. Similarly, 1b produced thioacetamide and tert-butylglyoxal, and 1c produced p-methoxy-thiobenzamide (and its S-oxide) and methylglyoxal. These results could be explained by the postulated metabolic pathways where thiazoles would undergo microsomal epoxidation of the C = C double bond and, after being hydrolyzed, the resulting epoxide would then be decomposed to form the corresponding thioamides and alpha-dicarbonyl fragments.

[Thioamine compound content in urine determined by using an iodine-azide reagent and selenious acid reaction]. / Soderzhanie tioaminosoedinenii v moche bol'nykh pri opredelenii s pomoshch'iu iod-azidnogo reagenta i po reaktsii s selenistoi kislotoi.

Iodine-azide reagent enabled to evaluate quantitatively content of thioamines excreted within a day. Concentration of thioketons in urine of patients was 11-15 microgram/eqv of thiourea per 1 ml, at the same time their excretion within a day accounted for 13.06 +/- 0.56 mg/eqv in women and 22.11 +/- 1.1 mg/eqv in men. Neither concentration of thioketones in urine nor their excretion in patients with various tumors studied were distinct from these patterns in urine of non-oncologic patients. Comparison of these two methods suggests that development of color on addition of selenous acid to urine is not due to reaction with thioamines present but to interaction with other unknown substances.