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Synthesis and antibacterial activity of quaternary ammonium compounds based on 3-hydroxypyridine

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Abstract

A library of 31 mono- and bis-quaternary ammonium compounds based on 3-hydroxypyridine was synthesized. Primary screening of their antibacterial activity in vitro in six archival strains of bacteria revealed four highly active lead compounds surpassing commercial antiseptics benzalkonium chloride, miramistin, and chlorhexidine in their activity. Further in-depth study of the antibacterial activity of the lead compounds in vitro in 16 clinical bacterial strains and the study of their toxicity in vitro and in vivo showed that 2,6-bis(N,N-dimethyl-N-dodecylammoniomethyl)-3-methoxypyridine dichloride was the most active and least toxic and manifested a higher activity in comparison with benzalkonium chloride, miramistin, and chlorhexidine in clinical isolate of both gram-positive and gram-negative bacteria, as well as a moderate toxicity in vivo (LD50 = 82 6 mg kg−1, mice, oral administration). The quaternary ammonium compounds based on 3-hydroxypyridine are of undoubted interest for the further development of antibacterial drugs.

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Authors and Affiliations

  1. Kazan (Volga Region) Federal University, 18 ul. Kremlevskaya, 420008, Kazan, Russian Federation

    N. V. Shtyrlin, R. M. Vafina, E. S. Bulatova, S. V. Sapozhnikov, L. E. Kalugin, M. R. Garipov, A. S. Yandimirova, T. V. Nikishova, M. N. Agafonova, R. R. Kazakova & Yu. G. Shtyrlin

  2. Kazan E. K. Zavoisky Physical-Technical Institute, Federal Research Center “Kazan Scientific Center of the Russian Academy of Sciences”, 10/7 ul. Sibirskiy trakt, 420029, Kazan, Russian Federation

    O. I. Gnezdilov

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  1. N. V. Shtyrlin
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  2. R. M. Vafina
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Correspondence to Yu. G. Shtyrlin.

Additional information

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2654–2669, December, 2022.

This work was supported by subsidy allocated to Kazan Federal University for the Russian state assignment in the sphere of scientific activities (Project No. 0671-2020-0053). O. I. Gnezdilov performed NMR measurements within the framework of the Russian state assignment to Federal Research Center “Kazan Scientific Center of the Russian Academy of Sciences”.

All procedures performed in the studies involving animals complied with the ethical standards of the Kazan (Volga Region) Federal University (Protocol No. 24 dated September 22, 2020 approved by the local ethics committee of KFU) and the legal acts of the Russian Federation and international organizations.

The authors declare no competing interests.

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Shtyrlin, N.V., Vafina, R.M., Bulatova, E.S. et al. Synthesis and antibacterial activity of quaternary ammonium compounds based on 3-hydroxypyridine. Russ Chem Bull 71, 2654–2669 (2022). https://doi.org/10.1007/s11172-022-3695-8

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