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2000
Volume 32, Issue 36
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Introduction

This work provides preclinical studies of an innovative antimicrobial agent named pyridosept, belonging to the quaternary bis-ammonium salts and synthesized on the base of pyridoxine. Since the wide spread of pathogens with tolerance to both antibiotics and antiseptics challenges the development of new antimicrobials providing high efficiency against fungi and microorganisms with multiple resistance.

Methods

This work presents studies of pyridosept, such as antibacterial and antifungal activities (determination of minimal inhibitory concentration and quantitative suspension test method), as well as antibacterial activity of metal surface test, sporicidal and spermicidal activities, formation of resistance (to bacteria and fungi), Skin-PAMPA (study of membrane transdermal permeability), mutagenicity assays (in Ames test and SOS-chromotest), cytotoxicity (MTT-assay) and comet assay in human skin fibroblasts.

Results

Pyridosept demonstrates advantageous antibacterial and antifungal activity in both suspension and metal surface tests; it has anti-SARS-CoV-2, spermicidal and sporicidal activities (comparable to chlorhexidine digluconate). On the other hand, it demonstrates a low frequency of bacterial resistance development (no more than 2-4-fold increase of the MIC in 30 passages, with MIC values fluctuating within 1-8 µg/ml for Gram-positive bacteria and 4-32 µg/ml for Gram-negative bacteria) and membrane transdermal permeability (Skin-PAMPA, 500-fold less compared to progesterone). While cytotoxicity (in MTT- and comet assay) of pyridosept is comparable with those for bezalkonium chloride and chlorhexidine, our results suggest that pyridosept represents an advantageous structure for the design of new antiseptics.

Conclusion

The information obtained during the studies demonstrated that pyridosept has a good efficacy and safety profile, which allows us to consider it as a potential antiseptic and disinfectant, for which it is necessary to conduct additional studies.

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2025-10-31

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References

  1. GerbaC.P. Quaternary ammonium biocides: Efficacy in application.Appl. Environ. Microbiol.201581246446910.1128/AEM.02633‑1425362069
     [Google Scholar]
  2. McDonnellG. RussellA.D. Antiseptics and disinfectants: Activity, action, and resistance.Clin. Microbiol. Rev.199912114717910.1128/CMR.12.1.1479880479
     [Google Scholar]
  3. ThomasL. RussellA.D. MaillardJ.Y. Antimicrobial activity of chlorhexidine diacetate and benzalkonium chloride against Pseudomonas aeruginosa and its response to biocide residues.J. Appl. Microbiol.200598353354310.1111/j.1365‑2672.2004.02402.x15715855
     [Google Scholar]
  4. TischerM. PradelG. OhlsenK. HolzgrabeU. Quaternary ammonium salts and their antimicrobial potential: Targets or nonspecific interactions?ChemMedChem201271223110.1002/cmdc.20110040422113995
     [Google Scholar]
  5. Bloomberg Lysol Sales Are Surging.Available from: https://www.bloomberg.com/news/articles/2020-04-30/lysol-maker-reckitt-benckiser-raises-outlook-after-sales-surge (Accessed 16 November 2023).2020
     [Google Scholar]
  6. Grand View Research, Antiseptic And Disinfectant Market Size & Share ReportAvailable from: https://www.grandviewresearch.com/industry-analysis/antiseptics-and-disinfectants-market (Accessed 16 November 2023).2023
     [Google Scholar]
  7. FedorowiczJ. SączewskiJ. Advances in the synthesis of biologically active quaternary ammonium compounds.Int. J. Mol. Sci.2024259464910.3390/ijms2509464938731869
     [Google Scholar]
  8. VereshchaginA.N. FrolovN.A. EgorovaK.S. SeitkalievaM.M. AnanikovV.P. Quaternary ammonium compounds (qacs) and ionic liquids (ils) as biocides: From simple antiseptics to tunable antimicrobials.Int. J. Mol. Sci.20212213679310.3390/ijms2213679334202677
     [Google Scholar]
  9. MohapatraS. YutaoL. GohS.G. NgC. LuhuaY. TranN.H. GinK.Y.H. Quaternary ammonium compounds of emerging concern: Classification, occurrence, fate, toxicity and antimicrobial resistance.J. Hazard. Mater.202344513039310.1016/j.jhazmat.2022.13039336455328
     [Google Scholar]
  10. ShtyrlinY.G. PetukhovA.S. StrelnikA.D. ShtyrlinN.V. IksanovaA.G. PugachevM.V. PavelyevR.S. DzyurkevichM.S. GaripovM.R. BalakinK.V. Chemistry of pyridoxine in drug design.Russ. Chem. Bull.201968591194510.1007/s11172‑019‑2504‑5
     [Google Scholar]
  11. ShtyrlinN.V. SapozhnikovS.V. GaliullinaA.S. KayumovA.R. BondarO.V. MirchinkE.P. IsakovaE.B. FirsovA.A. BalakinK.V. ShtyrlinY.G. Synthesis and antibacterial activity of quaternary ammonium 4-deoxypyridoxine derivatives.Biomed. Res. Int.20162016386419310.1155/2016/3864193
     [Google Scholar]
  12. ShtyrlinN. SapozhnikovS. KoshkinS. IksanovaA. SabirovA. KayumovA. NureevaA. ZeldiM. ShtyrlinY. Synthesis and antibacterial activity of novel quaternary ammonium pyridoxine derivatives.Med. Chem.201511765666510.2174/157340641166615050412293025938426
     [Google Scholar]
  13. SapozhnikovS.V. ShtyrlinN.V. KayumovA.R. ZamaldinovaA.E. IksanovaA.G. NikitinaЕ.V. KrylovaЕ.S. GrishaevD.Y. BalakinK.V. ShtyrlinY.G. New quaternary ammonium pyridoxine derivatives: Synthesis and antibacterial activity.Med. Chem. Res.201726123188320210.1007/s00044‑017‑2012‑9
     [Google Scholar]
  14. Antiseptic drug.Patent RU 2641309.2018Available from: https://patents.google.com/patent/RU2641309C1/ru
  15. ShtyrlinN.V. PugachevM.V. SapozhnikovS.V. GaripovM.R. VafinaR.M. GrishaevD.Y. PavelyevR.S. KazakovaR.R. AgafonovaM.N. IksanovaA.G. LisovskayaS.A. ZeldiM.I. KrylovaE.S. NikitinaE.V. SabirovaA.E. KayumovA.R. ShtyrlinY.G. Novel bis-ammonium salts of pyridoxine: Synthesis and antimicrobial properties.Molecules20202518434110.3390/molecules2518434132971844
     [Google Scholar]
  16. SchrankC.L. MinbioleK.P.C. WuestW.M. Are quaternary ammonium compounds, the workhorse disinfectants, effective against severe acute respiratory syndrome-coronavirus-2?ACS Infect. Dis.2020671553155710.1021/acsinfecdis.0c0026532412231
     [Google Scholar]
  17. KazakovaR.R. AgafonovaM.N. KazakovaF.F. IksanovaA.G. Questions of the pre-clinical research of antiseptics.Russian Journal of Biopharmaceuticals20191115660
     [Google Scholar]
  18. FDA, Safety and Effectiveness for Health Care Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use (Final Rule).Available from: https://www.fda.gov/about-fda/economic-impact-analyses-fda-regulations/safety-and-effectiveness-health-care-antiseptics-topical-antimicrobial-drug-products-over-counter (accessed 16 November 2023).2019
     [Google Scholar]
  19. World Health Organization, eEML - Electronic Essential Medicines List.Available from: https://list.essentialmeds.org/ (Accessed 16 November 2023).2023
     [Google Scholar]
  20. Method of producing 5,8-(bis(methylene(n,n-dimethyl-n- dodecylammonium))-2-ethyl-4h-[1,3]dioxino[4,5-c]pyridinium dichloride.Patent RU26978482017
  21. The State Pharmacopoeia of Russian Federation Ministry of public health of Russian Federation.14th edMoscow2018
     [Google Scholar]
  22. CLSI document M07-A9, 2012. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Ninth Edition. Wayne.J. Biosc. Med.201251
     [Google Scholar]
  23. AgafonovaM.N. Antibacterial activity profile of miramistin in in vitro and in vivo models.Microb. Pathog.202014210407210.1016/j.micpath.2020.104072
     [Google Scholar]
  24. Chemical disinfectants and antiseptics — Quantitative suspension test for the evaluation of bactericidal activity in the medical area— Test method and requirements (phase 2, step 1)EN 13727+A2:20152015
  25. Chemical disinfectants and antiseptics, Basic bactericidal activity-test method and requirements (phase 1) German version.EN 1040:19971997
  26. Chemical disinfectants and antiseptics ― Application of European Standards for chemical disinfectants and antiseptics.EN 14885:20152015
  27. MüllerG. KramerA. In vitro action of a combination of selected antimicrobial agents and chondroitin sulfate.Chem. Biol. Interact.20001242778510.1016/S0009‑2797(99)00142‑810670820
     [Google Scholar]
  28. Guidance 4.2.1890-04 Determination of the sensitivity of microorganisms to antibacterial drugs.Available from: https://docs.cntd.ru/document/1200038583 (Accessed 16 November 2023). 2008
     [Google Scholar]
  29. GuidanceR. Methods of laboratory research and testing of disinfectants to assess their effectiveness and safety.2010Available from: https://docs.cntd.ru/document/1200086231 (Accessed 16 November 2023).
     [Google Scholar]
  30. Methodological recommendations No. 2 Mycological examination of environmental objects and determination of antifungal activity of various substances. St. Petersburg: Ed. SPbMAPO House.2008
     [Google Scholar]
  31. Chemical disinfectants and antiseptics — Quantitative suspension test for the evaluation of fungicidal activity of chemical disinfectants and antiseptics used in food, industrial, domestic, and institutional areas — Test method and requirements (phase 2, step 1).EN 1650:20132013
  32. Chemical disinfectants and antiseptics — Quantitative non-porous surface test for the evaluation of bactericidal and/or fungicidal activity of chemical disinfectants used in food, industrial, domestic and institutional areas — Test method and requirements without mechanical action (phase 2, step 2).BS EN 13697:20152015
  33. MerkulevaI.A. ShcherbakovD.N. BorgoyakovaM.B. IsaevaA.A. NesmeyanovaV.S. VolkovaN.V. AripovV.S. ShanshinD.V. KarpenkoL.I. BelenkayaS.V. KazachinskaiaE.I. VolosnikovaE.A. EsinaT.I. SergeevA.A. TitovaK.A. KonyakhinaY.V. ZaykovskayaA.V. PyankovO.V. KolosovaE.A. ViktorinaO.E. ShelembaA.A. RudometovA.P. IlyichevA.A. Are hamsters a suitable model for evaluating the immunogenicity of rbd-based anti-COVID-19 subunit vaccines?Viruses2022145106010.3390/v1405106035632800
     [Google Scholar]
  34. SachsL. Statistische Auswertungsmethoden.Berlin/Heidelberg, GermanySpringer197210.1007/978‑3‑662‑10037‑0
     [Google Scholar]
  35. ErnyR. PorteH. [Efficacy of spermicides].Contracept. Fertil. Sex.199119428929112343221
     [Google Scholar]
  36. JoynsonJ.A. ForbesB. LambertR.J.W. Adaptive resistance to benzalkonium chloride, amikacin and tobramycin: The effect on susceptibility to other antimicrobials.J. Appl. Microbiol.20029319610710.1046/j.1365‑2672.2002.01667.x12067378
     [Google Scholar]
  37. RittiéL. FisherG.J. Isolation and Culture of Skin Fibroblasts.Fibrosis Research. VargaJ. BrennerD.A. PhanS.H. Totowa, NJHumana Press2005839810.1385/1‑59259‑940‑0:083
     [Google Scholar]
  38. McCannJ. AmesB.N. A simple method for detecting environmental carcinogens as mutagens.Ann. N. Y. Acad. Sci.1976271151310.1111/j.1749‑6632.1976.tb23086.x793475
     [Google Scholar]
  39. BogachevM.I. VolkovV.Y. MarkelovO.A. TriznaE.Y. BaydamshinaD.R. MelnikovV. MurtazinaR.R. ZelenikhinP.V. SharafutdinovI.S. KayumovA.R. Fast and simple tool for the quantification of biofilm-embedded cells sub-populations from fluorescent microscopic images.PLoS One2018135e019326710.1371/journal.pone.019326729715298
     [Google Scholar]
  40. OdaY. NakamuraS. OkiI. KatoT. ShinagawaH. Evaluation of the new system (umu-test) for the detection of environmental mutagens and carcinogens.Mutat. Res. Envir. Mutag. Relat. Subj.1985147521922910.1016/0165‑1161(85)90062‑73900709
     [Google Scholar]
  41. MillerJ. Experiments in Molecular Genetics: Assay of β- Galactosidase.Cold Spring Harbor Laboratory PressNew York1972
     [Google Scholar]
  42. FedorovaK. KayumovA. WoydaK. IlinskajaO. ForchhammerK. Transcription factor TnrA inhibits the biosynthetic activity of glutamine synthetase in Bacillus subtilis.FEBS Lett.201358791293129810.1016/j.febslet.2013.03.01523535029
     [Google Scholar]
  43. SinghN.P. McCoyM.T. TiceR.R. SchneiderE.L. A simple technique for quantitation of low levels of DNA damage in individual cells.Exp. Cell Res.1988175118419110.1016/0014‑4827(88)90265‑03345800
     [Google Scholar]
  44. NikitinaE.V. ZeldiM.I. PugachevM.V. SapozhnikovS.V. ShtyrlinN.V. KuznetsovaS.V. EvtyginV.E. BogachevM.I. KayumovA.R. ShtyrlinY.G. Antibacterial effects of quaternary bis-phosphonium and ammonium salts of pyridoxine on Staphylococcus aureus cells: A single base hitting two distinct targets?World J. Microbiol. Biotechnol.2016321510.1007/s11274‑015‑1969‑026712620
     [Google Scholar]
  45. WesselsS. IngmerH. Modes of action of three disinfectant active substances: A review.Regul. Toxicol. Pharmacol.201367345646710.1016/j.yrtph.2013.09.00624080225
     [Google Scholar]
  46. CayM.P.H. SosaO.A.A. FlemingG.T.A. Effect of subinhibitory concentrations of benzalkonium chloride on the competitiveness of Pseudomonas aeruginosa grown in continuous culture.Microbiology20101561303810.1099/mic.0.029751‑019815578
     [Google Scholar]
  47. PangZ. RaudonisR. GlickB.R. LinT.J. ChengZ. Antibiotic resistance in Pseudomonas aeruginosa: Mechanisms and alternative therapeutic strategies.Biotechnol. Adv.201937117719210.1016/j.biotechadv.2018.11.01330500353
     [Google Scholar]
  48. HeG.X. LandryM. ChenH. ThorpeC. WalshD. VarelaM.F. PanH. Detection of benzalkonium chloride resistance in community environmental isolates of staphylococci.J. Med. Microbiol.201463573574110.1099/jmm.0.073072‑024586033
     [Google Scholar]
  49. HegstadK. LangsrudS. LunestadB.T. ScheieA.A. SundeM. YazdankhahS.P. Does the wide use of quaternary ammonium compounds enhance the selection and spread of antimicrobial resistance and thus threaten our health?Microb. Drug Resist.20101629110410.1089/mdr.2009.012020370507
     [Google Scholar]
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Evaluation of Antiseptic Drug Candidate Pyridosept in Preclinical in Vitro Studies
Curr. Med. Chem. 32, 8171 (2025); https://doi.org/10.2174/0109298673356654250122063321
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  • Article Type:     Research Article
Keyword(s): antiseptics; benzalkonium chloride; chlorhexidine digluconate; infectious diseases; miramistin; Pyridosept

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