Medicinal Chemistry Research

, Volume 26, Issue 12, pp 3188–3202 | Cite as

New quaternary ammonium pyridoxine derivatives: synthesis and antibacterial activity

  • Sergey V. Sapozhnikov
  • Nikita V. Shtyrlin
  • Airat R. Kayumov
  • Alina E. Zamaldinova
  • Alfiya G. Iksanova
  • Еlena V. Nikitina
  • Еlena S. Krylova
  • Denis Yu. Grishaev
  • Konstantin V. Balakin
  • Yurii G. Shtyrlin
Original Research

Abstract

A diverse library of 34 new quaternary mono-ammonium and bis-ammonium pyridoxine derivatives was synthesized, and their antibacterial activity against several clinically relevant bacterial strains was evaluated in vitro. Several mono-ammonium compounds demonstrated high antibacterial activity against methicillin-resistant Staphylococcus strains with minimum inhibitory concentrations in the range of 0.5–8 µg/mL, which exceeded activity of miramistin and was comparable to that of benzalkonium chloride. SOS-chromotest in Salmonella typhimurium showed the lack of DNA-damage activity for all active compounds. A clear correlation has been observed between the lipophilicity of the obtained compounds and their activity against the studied Gram-positive bacterial strains. Cytotoxicity studies on HEK-293 cells demonstrated that some of the active compounds were less toxic than the reference drugs. Antibacterial activity studies in the presence of CaCl2 suggested that the cell wall damage associated with the removal of Ca2+ ions from the bacterial membrane is one of the possible mechanisms of antibacterial activity. The obtained results make the described active compounds a promising starting point for the development of new antibacterial therapies.

Keywords

Quaternary ammonium salts Pyridoxine Antibacterial activity Cytotoxicity Genotoxicity Cell wall damaging agents 

Notes

Acknowledgements

This work was funded by the subsidy allocated to Kazan Federal University by Federal Targeted Programme for Research and Development in Priority Areas of Development of the Russian Scientific and Technological Complex for 2014-2020 (Project №14.575.21.0037 from 27.06.2014, the unique identifier of the agreement RFMEF157514X0037).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_2012_MOESM1_ESM.docx (20.9 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Sergey V. Sapozhnikov
    • 1
  • Nikita V. Shtyrlin
    • 1
  • Airat R. Kayumov
    • 1
  • Alina E. Zamaldinova
    • 1
  • Alfiya G. Iksanova
    • 1
  • Еlena V. Nikitina
    • 1
  • Еlena S. Krylova
    • 1
  • Denis Yu. Grishaev
    • 1
  • Konstantin V. Balakin
    • 1
    • 2
  • Yurii G. Shtyrlin
    • 1
  1. 1.Kazan (Volga region) Federal UniversityKazanRussia
  2. 2.I.M. Sechenov First Moscow State Medical UniversityMoscowRussia

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