Novel pyridyl-substituted nitronyl nitroxides as potential antiarrhythmic and hypotensive agents with low toxicity and enhanced stability in aqueous solutions.

Autor: Kolesnikov AE; N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, Moscow, 119991, Russia. Electronic address: a.kolesnikov@ioc.ac.ru., Bryzgalov AO; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Russian Academy of Sciences, Siberian Branch, Akademika Lavrentieva prospect 9, Novosibirsk, 630090, Russia. Electronic address: arkadiy@nioch.nsc.ru., Tolstikov SE; N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, Moscow, 119991, Russia; International Tomography Center, Russian Academy of Sciences, Siberian Branch, Institutskaya ulitsa 3a, Novosibirsk, 630090, Russia., Yanshole VV; International Tomography Center, Russian Academy of Sciences, Siberian Branch, Institutskaya ulitsa 3a, Novosibirsk, 630090, Russia., Romanenko GV; International Tomography Center, Russian Academy of Sciences, Siberian Branch, Institutskaya ulitsa 3a, Novosibirsk, 630090, Russia., Letyagin GA; International Tomography Center, Russian Academy of Sciences, Siberian Branch, Institutskaya ulitsa 3a, Novosibirsk, 630090, Russia., Smirnova KA; International Tomography Center, Russian Academy of Sciences, Siberian Branch, Institutskaya ulitsa 3a, Novosibirsk, 630090, Russia., Tolstikova TG; N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Russian Academy of Sciences, Siberian Branch, Akademika Lavrentieva prospect 9, Novosibirsk, 630090, Russia., Bogomyakov AS; N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, Moscow, 119991, Russia; International Tomography Center, Russian Academy of Sciences, Siberian Branch, Institutskaya ulitsa 3a, Novosibirsk, 630090, Russia., Ovcharenko VI; N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, Moscow, 119991, Russia; International Tomography Center, Russian Academy of Sciences, Siberian Branch, Institutskaya ulitsa 3a, Novosibirsk, 630090, Russia.
Jazyk: angličtina
Zdroj: Nitric oxide : biology and chemistry [Nitric Oxide] 2024 Feb 01; Vol. 143, pp. 9-15. Date of Electronic Publication: 2023 Dec 12.
DOI: 10.1016/j.niox.2023.12.001
Abstrakt: This study explores the antiarrhythmic and hypotensive potential of pyridyl-substituted nitronyl nitroxides derivatives, uncovering the crucial role of a single carbon moiety of the pyridine cycle alongside radical and charged oxygen centers of the imidazoline fragment. Notably, the introduction of fluorine atoms diminished the antiarrhythmic effect, while the most potent derivatives featured the nitronyl nitroxide pattern positioned at the third site of the pyridine cycle. Gender-dependent responses were observed in lead compounds L CF 3 and L Me , with L Me inducing temporary bradycardia and hypotension specifically in female rats, and L CF3 causing significant blood pressure reduction followed by rebound in females compared to milder effects in males. Mechanistic insights point towards β 1 adrenoceptor blockade as an underlying mechanism, supported by experiments on isolated rat atria. This research underscores the interplay between structure, cardiovascular effects and gender-specific responses, offering insights for therapeutic strategies for treating free radical-associated cardiovascular disorders.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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