New Donors and Acceptors of Nitrogen Oxide as Potential Therapeutic Agents |
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Authors: | V. I. Yelinova A. A. Bobko D. G. Mazhukin A. L. Markel V. V. Khramtsov |
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Affiliation: | (1) Institute of Chemical Kinetics and Combustion, Siberian Division, Russian Academy of Sciences, ul. Institutskaya 3, Novosibirsk, 630090, Russia;(2) Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, pr. Akademika Lavrent'eva 9, Novosibirsk, 630090, Russia;(3) Institute of Cytology and Genetics, Siberian Division, Russian Academy of Sciences, pr. Akademika Lavrent'eva 10, Novosibirsk, 630090, Russia |
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Abstract: | The synthesis of new donors and acceptors of nitrogen oxide is described. New lipophilic nitronylnitroxyl radicals (NNR) that act as paramagnetic scavengers of nitrogen oxide are synthesized and characterized. The purity of the preparations is determined, and their structures are confirmed. The lipophilicity of the radicals is tested by ESR spectroscopy. The incorporation into lipid multilayers is shown to protect NNR from reduction in biological samples, while their ability to scavenge nitrogen oxide and form iminonitroxyl radicals is retained. A decreased rate of NNR reduction under these conditions substantially enhances their effectiveness as paramagnetic acceptors of nitrogen oxide in biological systems. The synthesis of a new hydrophilic NO donor, 3-bromo-3,4-dihydro-4,4-dimethyl-3-(2-pyridyl)-diazet-1,2-dioxide (DDpyr), is described. The constants of DDpyr decomposition in tris-HCl buffer (pH 7.5) and in DMSO are determined (4.5 × 10–6 and 0.5 × 10–6 s–1, respectively). A substantially higher rate of DDpyr decomposition in buffer, compared with the decomposition rates determined previously for some diazetines, makes DDpyr a prospective candidate for the use in aqueous media. It is found in experiments on perfused rat caudal artery that DDpyr is an effective vasodilator. Intraperitoneal injection of DDpyr to hereditarily hypertensive rats (ISIAH line) at doses of 100–200 g/kg body mass considerably diminishes their systolic arterial pressure. |
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Keywords: | acceptors of nitrogen oxide arterial pressure donors of nitrogen oxide nitronylnitroxyl radical nitrogen oxide vasodilators |
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