دورية أكاديمية
[Radioprotective properties of isothiourea derivatives with NO-inhibitory mechanism of action].
| العنوان: | [Radioprotective properties of isothiourea derivatives with NO-inhibitory mechanism of action]. |
|---|---|
| المؤلفون: | Filimonova MV, Proskuriakov SIa, Shevchenko LI, Shevchuk AS, Lushnikova GA, Makarchuk VM, Arzamastsev EV, Laba VI, Malinovskaia KI, Levitskaia EL |
| المصدر: | Radiatsionnaia biologiia, radioecologiia [Radiats Biol Radioecol] 2012 Nov-Dec; Vol. 52 (6), pp. 593-601. |
| نوع المنشور: | English Abstract; Journal Article |
| اللغة: | Russian |
| بيانات الدورية: | Publisher: Nauka Country of Publication: Russia (Federation) NLM ID: 9317212 Publication Model: Print Cited Medium: Print ISSN: 0869-8031 (Print) Linking ISSN: 08698031 NLM ISO Abbreviation: Radiats Biol Radioecol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Moskva : Nauka, 1993- |
| مواضيع طبية MeSH: | Nitric Oxide Synthase*/antagonists & inhibitors , Nitric Oxide Synthase*/metabolism , beta-Aminoethyl Isothiourea*/administration & dosage , beta-Aminoethyl Isothiourea*/analogs & derivatives , beta-Aminoethyl Isothiourea*/chemical synthesis, Radiation-Protective Agents/*administration & dosage, Animals ; Enzyme Inhibitors/administration & dosage ; Gamma Rays ; Lethal Dose 50 ; Mice ; Radiation-Protective Agents/chemical synthesis |
| مستخلص: | The study of the radioprotective activity of S-[2-alkyl (aryl) sulfonyl]-S-ethyl derivatives of (vinyl)-isothiourea in (he model of the survival of mice exposed to gamma-radiation at a dose of 10 Gy has shown that the incorporation of additional sulfur-containing groups does not increase the radioprotective properties of compounds. In contrast to aminoalkil thiols, the effectiveness of the radiation protection action of the isothiourea (ITU) derivatives studied clearly correlates with the NO-inhibitory activity. This fact allowed us to assume that the radioprotective effect of S-substituted ITU caused inhibition of the endogenous synthesis of NO, which promotes the development of circulatory hypoxia, and that a further search for the radioprotective agents in this class of chemicals should be considered as the search for effective inhibitors of NO-synthase (NOS). The theoretical analysis of the conformity of molecular structures to the composition and topology of the active center of NOS-inhibitors allowed us to prognosticate a number of new ITU derivatives with the potential NOS-inhibiting ability. As a result of further theoretical and experimental studies, four S,N-disubstituted ITU derivatives - active non-selective NOS-inhibitors, were first identified and synthesized. These compounds exhibited a pronounced and prolonged vasopressive effects at doses of 0.01-0.05 LD50/15 in the models of severe hemorrhagic and endotoxic shock, and provided 65-100% 30-day survival at doses of 0.2-0.3 LD50/15 in the mice irradiated by gamma-rays at a dose of 10 Gy (LD98/30).The findings suggest the pronounced radioprotective effect of NOS-inhibitors among the ITU-derivatives. |
| المشرفين على المادة: | 0 (Enzyme Inhibitors) 0 (Radiation-Protective Agents) 151-16-6 (beta-Aminoethyl Isothiourea) EC 1.14.13.39 (Nitric Oxide Synthase) |
| تواريخ الأحداث: | Date Created: 20130323 Date Completed: 20130426 Latest Revision: 20161020 |
| رمز التحديث: | 20231215 |
| PMID: | 23516890 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0869-8031 |
|---|