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

Journal Nitric Oxide
ISSN: 1089-8603
Output data Year: 2024, Volume: 143, Pages: 9-15 Pages count : 7 DOI: 10.1016/j.niox.2023.12.001
Authors Kolesnikov Andrey E. 1 , Bryzgalov Arkadiy O. 2 , Tolstikov Svyatoslav E. 3,1 , Yanshole Vadim V. 3 , Romanenko Galina V. 3 , Letyagin Gleb A. 3 , Smirnova Kristina A. 3 , Tolstikova Tatiana G. 2 , Bogomyakov Artem S. 3,1 , Ovcharenko Victor I. 3,1
Affiliations
1 N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow, 119991, Russia
2 N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Russian Academy of Sciences, Siberian Branch, Akademika Lavrentieva Prospect 9, Novosibirsk, 630090, Russia
3 International Tomography Center, Russian Academy of Sciences, Siberian Branch, Institutskaya Ul. 3a, Novosibirsk, 630090, Russia

Abstract: 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 LCF3 and LMe, with LMe inducing temporary bradycardia and hypotension specifically in female rats, and LCF3 causing significant blood pressure reduction followed by rebound in females compared to milder effects in males. Mechanistic insights point towards β1 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.
Cite: Kolesnikov A.E. , Bryzgalov A.O. , Tolstikov S.E. , Yanshole V.V. , Romanenko G.V. , Letyagin G.A. , Smirnova K.A. , Tolstikova T.G. , Bogomyakov A.S. , Ovcharenko V.I.
Novel pyridyl-substituted nitronyl nitroxides as potential antiarrhythmic and hypotensive agents with low toxicity and enhanced stability in aqueous solutions
Nitric Oxide. 2024. V.143. P.9-15. DOI: 10.1016/j.niox.2023.12.001 WOS Scopus OpenAlex
Identifiers:
Web of science: WOS:001144172100001
Scopus: 2-s2.0-85183466231
OpenAlex: W4389616777
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