Interaction of <i>N</i>-alkyl-<i>N</i>-nitrosourethanes with thiols

Schoental, R.; Rive, DJ

doi:10.1042/bj0970466

Cited by 54 publications

(12 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…H n contrast, nitrosarnides such as the N-nitrosoguanidines evaluted in this study are unstable at physiological pH and can decompose noncnzymatically to yield reactive species, particcalarly in the presence of thiols (Lawley and Thatcher 1970;McCalla 46 a / . 1968: Schoental andRive 1965;Schultz and McCalla 1969;Wheeler and Bcswdsn 1972). Interactions between nitr~asoguanidines and thiols can result in the release of nltric oxide (Hgnano er a / .…”

Section: Elvngmentioning

confidence: 99%

Vasodilator actions of several N-nitroso compounds

Lippton¹,

Gruetter²,

Ignarro³

et al. 1982

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

Recent studies have shown that N-nitroso compounds can activate arterial guanylate cyclase and relax isolated arterial smooth muscle; however, the effects of these substances on the cardiovascular system in the anesthetized cat are unknown. The present study was undertaken to compare the effects of several nitrosoguanidines and a nitrosamine, N-nitrosodimethylamine, on arterial guanylate cyclase activity, isolated arterial smooth muscle tone, and systemic vascular resistance in the anesthetized cat. Intravenous injections and infusions of the nitrosoguanidines glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) decreased systemic arterial pressure. During intravenous infusion of the nitrosoguanidines GTN and SNP, cardiac output was unchanged at the peak of the decrease in aortic pressure, indicating that the nitrosoguanidines GTN and SNP both reduced systemic vascular resistance. In addition, intraarterial injections of the nitrosoguanidines produced dose-dependent decreases in perfusion pressure in the feline mesenteric vascular bed perfused at constant flow. These substances were potent relaxants of isolated arterial smooth muscle and markedly activated arterial guanylate cyclase. In contrast, N-nitrosodimethylamine was devoid of vasodilator activity in vivo and exerted only minimal effects on isolated arterial smooth muscle tone or on arterial guanylate cyclase activity. The present data demonstrate a relationship between guanylate cyclase activation and arterial smooth muscle relaxation and suggest that the vasodilator effects on resistance vessels in vivo in response to selected N-nitroso compounds may involve such a mechanism. Although the significance of the presently reported cardiovascular responses to N-nitroso compounds is uncertain, N-nitroso compounds may represent a previously unrecognized class of substances which can be formed in the body and which possess marked vasodilator activity. It is possible that this vasodilator activity may involve the relaxation of vascular smooth muscle through activation of guanylate cyclase.

show abstract

Section: Elvngmentioning

confidence: 99%

Vasodilator actions of several N-nitroso compounds

Lippton¹,

Gruetter²,

Ignarro³

et al. 1982

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…The interaction of N-methyl-N-nitrosourethane with cysteine in aqueous ethanol at room temperature is reported to afford a variety of compounds arising from nucleophilic attack of the thiol on the carbonyl group. Denitrosation reactions were not considered (24). We have conducted preliminary experiments in which N-methyl-Nnitrosourethane and N-methyl-N-nitrosourea in their reactions with cysteine in aqueous ethanol failed to yield any of the red color characteristic of S-nitroso compounds.…”

Section: Reactions Of Cysteine With Ngmentioning

confidence: 99%

Reactions of cysteine with N-methyl-N-nitroso-p-toluenesulfonamide and N-methyl-N′-nitro-N-nitrosoguanidine

Schulz¹,

McCalla²

1969

Can. J. Chem.

View full text Add to dashboard Cite

The reaction between cysteine and N-methyl-N-nitroso-p-toluenesulfonamide affords almost quantitative yields of cystine and N-methyl-p-toluenesuIfonaniide. A mechanism based on the intermediacy of the S-nitroso derivative of cysteine and the intermediate formation of nitric oxide is proposed. Nitrous oxide is shown to be a final product. In the reaction of cysteine with N-methyl-N'-nitro-N-nitrosoguanidine a substantial yield of 2-nitramino-4-carboxyl-thiazoline is obtained. Cystine, N-methyl-N'-nitroguanidine and S-methylcysteine are formed in lesser amounts. The major product arises from nucleophilic attack on the iniino carbon of N-methyl-N'-nitro-N-nitrosoguanidine. Concomitant elimination of the methylnitrosamino group accounts for the methylating ability of the system. Canadian Journal of Chemistry, 47, 2021 (1969) Previous work in this laboratory has shown that deoxyribonucleic acid (DNA) becomes methylated when it is allowed to react in vitro with either N-methyl-N'-nitro-N-nitrosoguanidine (NG) or with N-methyl-N-nitroso-p-toluenesulfonamide (MNTS) (1). Addition of cysteine to the reaction mixture was found to increase methylation by N G but to decrease dramatically methylation by MNTS, results which are of considerable interest in view of biological studies showing that cysteine has a protective action against certain types of alkylating agents (2).Both N G and MNTS are well-established sources of diazomethane in their reactions with aqueous base (3,4). For the reactions of N G and MNTS with nucleophilic reagents other than oxygen nucleophiles, a variety of products are reported. McKay and Wright (5) demonstrated that primary alkyl or aryl amines react with N G with the elimination of the methylnitrosamino group and the formation of N-substituted nitroguanidines. The only secondary amine to react with N G to give a Ndisubstituted-Nf-nitroguanidine is dimethylamine. Reaction of N G with other secondary amines resulted in denitrosation (6). In the reaction of N G with azide ion the methylnitrosamino group is eliminated and 5-nitroaminotetrazole is formed by cyclization of the intermediate nitrogiianylazide (7). The reaction between MNTS and piperidine results in transfer of the nitroso group to form N-nitrosopiperidine without the formation of any diazomethane (4). Low yields of diphenylnitrosamine are reported to result from reaction of MNTS with diphenylamine (8).Thus, while the existing literature pointed to the fact that the N-methyl-N-nitroso compounds under consideration exhibit two centers susceptible to nucleophilic attack, resulting in loss of the methylnitrosamino group and the nitroso function respectively, no information was available on their reactions with mercaptans. We report here data that provide a reasonable explanation for the difference in the behavior of N G and MNTS in the presence of cysteine. Results and Discussion Reactions of Cysteitze rvith M N T SThe reactions of cysteine with MNTS were carried out at room temperature in aqueous 25 % ethanol at pH 7 in an atmosphere of nit...

show abstract

“…Recent studies indicate that the breakdown products of nitrosamides and nitrosamidines may be dependent upon the medium in which the compounds are maintained. Complex mixtures of reaction products may appear under physiological conditions (31,37,38), probably as a result of competing or linked reactions. These reaction products may induce significant biological consequences of their own.…”

Section: Resltsmentioning

confidence: 99%

“…These reaction products may induce significant biological consequences of their own. It has been suggested (19,23,37) that activation of the nitrosamidines and nitrosamides may be accomplished through loss of their nitroso group. The nitroso group may be rapidly converted into nitrous acid with the subsequent formation of hydroxylamines and hydrazines which are highly active biologically.…”

Section: Resltsmentioning

confidence: 99%