A set of new quaternary ammonium compounds based on pyridine-4-aldoxime was synthesized, characterized with analytical data (NMR, EA, HPLC, MS) and tested for in vitro antimicrobial activity (antibacterial, antifungal) and cytotoxicity. Quaternary pyridinium-4-aldoxime salts with length of alkyl side chain from C8 to C20 and belonging to the group of cationic surfactants were investigated in this work. An HPLC experimental protocol for characterization of mixtures of all homologues has been found. Antimicrobial evaluation found that yeast-type fungi were most sensitive towards C14 and C16 analogues, whereas the C16 analogue was completely ineffective against filamentous fungi. Antibacterial assessment showed versatility of C14 and relatively high efficacy of C16 against G+ strains and C14 against G- strains. Notably, none of the studied compounds exceeded the efficacy and versatility of the benzalkonium C12 analogue, and benzalkonium analogues also exhibited lower cytotoxicity in the cell viability assay.

Biomedical Research Centre University Hospital Hradec Kralove Sokolska 581 Hradec Kralove 500 05 Czech Republic

Department of Cybernetics and Biomedical Engineering Faculty of Electrical Engineering and Computer Science VSB Technical University of Ostrava 17 Listopadu 15 Ostrava Poruba 708 33 Czech Republic

Department of Epidemiology Faculty of Military Health Sciences University of Defence Trebesska 1575 Hradec Kralove 500 01 Czech Republic

Department of Medicinal Chemistry and Drug Analysis Faculty of Pharmacy Charles University Prague Heyrovskeho 1203 Hradec Kralove 500 05 Czech Republic

Department of Toxicology and Military Pharmacy Faculty of Military Health Sciences University of Defence Trebesska 1575 Hradec Kralove 500 01 Czech Republic

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Singh S., Bhadani A., Kataria H., Kaur G., Kamboj R. Synthesis of glycerol-based pyridinium surfactants and appraisal of their properties. Ind. Eng. Chem. Res. 2009;48:1673–1677. doi: 10.1021/ie801737m. DOI

Earle M.J., Katdare S.P., Seddon K.R. Paradigm confirmed: The first use of ionic liquids to dramatically influence the outcome of chemical reactions. Org. Lett. 2004;6:707–710. doi: 10.1021/ol036310e. PubMed DOI

Price P.B. Benzalkonium chloride (zephiran chloride) as a skin disinfectant. Arch. Surg. 1950;61:23–33. doi: 10.1001/archsurg.1950.01250020026004. PubMed DOI

Semmler A., Kohler H.H. Surface properties of alkylpyridinium chlorides and the applicability of the pendant drop technique. J. Colloid Interface Sci. 1999;218:137–144. doi: 10.1006/jcis.1999.6413. PubMed DOI

Akbas H., Kartal C.C.I. Reactive orange 16-dodecylpyridinium chloride interactions in electrolytic solutions. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2006;65:95–99. doi: 10.1016/j.saa.2005.09.033. PubMed DOI

Rodriguez-Morales S., Compadre R.L., Castillo R., Breen P.J., Compadre C.M. 3D-QSAR, synthesis, and antimicrobial activity of 1-alkylpyridinium compounds as potential agents to improve food safety. Eur. J. Med. Chem. 2005;40:840–849. doi: 10.1016/j.ejmech.2005.02.012. PubMed DOI

Sivak A., Goyer M., Perwak J., Thayer P. Environmental and Human Health Aspects of Commercially Important Surfactants. In: Mittal K.L., Fendler E.J., editors. Solution Behaviour of Surfactants (Theoretical and Applied Aspects) Volume 1. Plenum Press; New York, NY, USA: 1982. pp. 161–188.

Kuca K., Bielavska M., Cabal J., Dohnal V. Determination of benzalkonium bromide homologues in disinfection products using high-performance liquid chromatography. Anal. Lett. 2005;38:673–682. doi: 10.1081/AL-200050326. DOI

Kuca K., Marek J., Stodulka P., Musilek K., Hanusova P., Hrabinova M., Jun D. Preparation of benzalkonium salts differing in the length of a side alkyl chain. Molecules. 2007;12:2341–2347. doi: 10.3390/12102341. PubMed DOI PMC

Wong Y.L., Hubieki M.P., Curfman C.L., Doncel G.F., Dudding T.C., Savle P.S., Gandour R.D. A structure-activity study of spermicidal and anti-hiv properties of hydroxylated cationic surfactants. Bioorg. Med. Chem. 2002;10:3599–3608. doi: 10.1016/S0968-0896(02)00245-6. PubMed DOI

Lin J., Qiu S.Y., Lewis K., Klibanov A.M. Bactericidal properties of flat surfaces and nanoparticles derivatized with alkylated polyethylenimines. Biotechnol. Prog. 2002;18:1082–1086. doi: 10.1021/bp025597w. PubMed DOI

Tiller J.C., Liao C.J., Lewis K., Klibanov A.M. Designing surfaces that kill bacteria on contact. Proc. Natl. Acad. Sci. USA. 2001;98:5981–5985. doi: 10.1073/pnas.111143098. PubMed DOI PMC

Faraj J.A., Dorati R., Schoubben A., Worthen D., Selmin F., Capan Y., Leung K., DeLuca P.P. Development of a peptide-containing chewing gum as a sustained release antiplaque antimicrobial delivery system. AAPS PharmSciTech. 2007;8:E177–E185. doi: 10.1208/pt0801026. PubMed DOI PMC

Tanzer J.M., Slee A.M., Kamay B., Scheer E.R. In vitro evaluation of seven cationic detergents as antiplaque agents. Antimicrob. Agents Chemother. 1979;15:408–414. doi: 10.1128/AAC.15.3.408. PubMed DOI PMC

Shelton R.S., Vancampen M.G., Tilford C.H., Lang H.C., Nisonger L., Bandelin F.J., Rubenkoenig H.L. Quaternary ammonium salts as germicides 1. Non-acylated quaternary ammonium salts derived from aliphatic amines. J. Am. Chem. Soc. 1946;68:753–755. PubMed

Li Y.B., Slavik M.F., Walker J.T., Xiong H. Pre-chill spray of chicken carcasses to reduce salmonella typhimurium. J. Food Sci. 1997;62:605–607. doi: 10.1111/j.1365-2621.1997.tb04441.x. DOI

Brill F., Goroncy-Bermes P., Sand W. Influence of growth media on the sensitivity of staphylococcus aureus and pseudomonas aeruginosa to cationic biocides. Int. J. Hyg. Environ. Health. 2006;209:89–95. doi: 10.1016/j.ijheh.2005.08.007. PubMed DOI

Dwars T., Paetzold E., Oehme G. Reactions in micellar systems. Angewa. Chem. Int. Ed. 2005;44:7174–7199. doi: 10.1002/anie.200501365. PubMed DOI

Ghosh K.K., Kolay S., Bal S., Satnami M.L., Quagliotto P., Dafonte P.R. Effect of cationic gemini surfactants on the hydrolysis of carboxylate and phosphate esters using hydroxamate ions. Coll. Polym. Sci. 2008;286:293–303. doi: 10.1007/s00396-007-1769-7. DOI

Ghosh K.K., Satnami M.L., Sinha D. Dephosphorylation of paraoxon by hydroxamate ions in micellar media. Tetrahedron. Lett. 2004;45:9103–9105. doi: 10.1016/j.tetlet.2004.10.023. DOI

Singh N., Ghosh K.K., Marek J., Kuca K. Hydrolysis of carboxylate and phosphate esters using monopyridinium oximes in cationic micellar media. Int. J. Chem. Kinet. 2011;43:569–578. doi: 10.1002/kin.20525. DOI

Cabal J., Kuca K., Sevelova-Bartosova L., Dohnal V. Cyclodextrines as functional agents for decontamination of the skin contaminated by nerve agents. Acta Medica (Hradec Kral.) 2004;47:115–118. PubMed

Tiwari S., Ghosh K.K., Marek J., Kuca K. Comparative study of nucleophilic efficacy of pralidoxime towards phosphorus, sulfur and thiophosphorus based esters. React. Kinet. Catal. Lett. 2009;98:91–97. doi: 10.1007/s11144-009-0072-7. DOI

Tiwari S., Ghosh K.K., Marek J., Kuca K. Functionalized surfactant mediated reactions of carboxylate, phosphate and sulphonate esters. J. Phys. Org. Chem. 2010;23:519–525. doi: 10.1002/poc.1635. DOI

Tiwari S., Ghosh K.K., Marek J., Kuca K. Cationic micellar-catalyzed hydrolysis of pesticide fenitrothion using alpha-nucleophiles. Lett. Drug Des. Discov. 2010;7:194–199. doi: 10.2174/157018010790596650. DOI

Tiwari S., Kolay S., Ghosh K.K., Kuca K., Marek J. Kinetic study of the reactions of p-nitrophenyl acetate and p-nitrophenyl benzoate with oximate nucleophiles. Int. J. Chem. Kinet. 2009;41:57–64. doi: 10.1002/kin.20363. DOI

Fisicaro E., Pelizzetti E., Viscardi G., Quagliotto P.L., Trossarelli L. Thermodynamic properties of aqueous micellar solutions of N-(1H,1H,2H,2H perfluorooctyl)pyridinium chloride and N-(1H,1H,2H,2H perfluorodecyl)pyridinium chloride. In: Franses E.I., Weers J.G., editors. Colloids and Surfaces A: Physicochemical and Engineering Aspects, Proceedings of the ACS Symposium on Colloid and Surface Chemistry of Fluorocarbons and Highly Fluorinated Amphiphiles at 205th Annual ACS Meeting; Denver, CO, USA. 28 March–2 April 1993; London, UK: Elsevier; 1994. pp. 59–70.

Fisicaro E., Ghiozzi A., Pelizzetti E., Viscardi G., Quagliotto P.L. Effect of the counterion on thermodynamic properties of aqueous micellar solutions of 1-(3,3,4,4,5,5,6,6,6-nonafluorohexyl) pyridinium halides: Ii. Apparent and partial molar enthalpies and osmotic coefficients at 313 k. J. Colloid Interface Sci. 1996;184:147–154. PubMed

Fisicaro E., Biemmi M., Compari C., Duce E., Peroni M. Thermodynamics of aqueous solutions of dodecyldimethylethylammonium bromide. J. Colloid Interface Sci. 2007;305:301–307. doi: 10.1016/j.jcis.2006.09.063. PubMed DOI

Kuca K., Kivala M., Dohnal V. A general method for the quaternization of N,N-dimethyl benzylamines with long chain N-alkylbromides. J. Appl. Biomed. 2004;2:195–198.

Spilovska K., Korabecny J., Kral J., Horova A., Musilek K., Soukup O., Drtinova L., Gazova Z., Siposova K., Kuca K. 7-Methoxytacrine-adamantylamine heterodimers as cholinesterase inhibitors in Alzheimer’s disease treatment—synthesis, biological evaluation and molecular modeling studies. Molecules. 2013;18:2397–2418. doi: 10.3390/molecules18022397. PubMed DOI PMC

Korabecny J., Soukup O., Dolezal R., Spilovska K., Nepovimova E., Andrs M., Nquyen T.D., Jun D., Musilek K., Kucerova-Chlupacova M., Kuca K. From pyridinium-based to central active acetylcholinesterase reactivators. Mini Rev. Med. Chem. 2014;14:215–221. doi: 10.2174/1389557514666140219103138. PubMed DOI

Malinak D., Dolezal R., Marek J., Salajkova S., Soukup O., Vejsova M., Korabecny J., Honegr J., Penhaker M., Musilek K., et al. 6-Hydroxyquinolinium salts differing in the length of alkyl side-chain: Synthesis and antimicrobial activity. Bioorg. Med. Chem. Lett. 2014;24:5238–5241. PubMed

Jordan D., Tan E., Hegh D. Synthesis, characterization and conductivity of quaternary nitrogen surfactants modified by the addition of a hydroxymethyl substructure on the head group. J. Surfactants Deterg. 2012;15:587–592. doi: 10.1007/s11743-012-1360-1. DOI

Kamboj R., Singh S., Chauhan V. Synthesis, characterization and surface properties of N-(2-hydroxyalkyl)-N'-(2-hydroxyethyl)imidazolium surfactants. Coll. Surf. A Physicochem. Eng. Asp. 2014;441:233–241. doi: 10.1016/j.colsurfa.2013.08.063. DOI

Li Y.L., Li Q.X., Zhi L.F., Zhang M.H. Synthesis, characterization and surface activity of trioctyl hydroxyethyl ammonium chloride. Tenside Surfactants Deterg. 2011;48:305–307. doi: 10.3139/113.110135. DOI

Marek J., Stodulka P., Cabal J., Soukup O., Pohanka M., Korabecny J., Musilek K., Kuca K. Preparation of the pyridinium salts differing in the length of the N-alkyl substituent. Molecules. 2010;15:1967–1972. doi: 10.3390/molecules15031967. PubMed DOI PMC

Marek J., Buchta V., Soukup O., Stodulka P., Cabal J., Ghosh K.K., Musilek K., Kuca K. Preparation of quinolinium salts differing in the length of the alkyl side chain. Molecules. 2012;17:6386–6394. doi: 10.3390/molecules17066386. PubMed DOI PMC

Coughlin R.T., Tonsager S., McGroarty E.J. Quantitation of metal-cations bound to membranes and extracted lipopolysaccharide of escherichia-coli. Biochemistry. 1983;22:2002–2007. doi: 10.1021/bi00277a041. PubMed DOI

McDonnell G., Russell A.D. Antiseptics and disinfectants: Activity, action, and resistance. Clin. Microbiol. Rev. 2001;14:227–228. PubMed PMC

Zhong X., Guo J.W., Fu S.Q., Zhu D.Y., Peng J.P. Synthesis, surface property and antimicrobial activity of cationic gemini surfactants containing adamantane and amide groups. J. Surfactants Deterg. 2014;17:943–950. doi: 10.1007/s11743-014-1580-7. DOI

Clinical and Laboratory Standards Institute (CLSI) Approved Standard-Third Edition. CLSI; Wayne, PA, USA: 2008. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts. CLSI document M27-A3.

Clinical and Laboratory Standards Institute (CLSI) Approved Standard-Second Edition. CLSI; Wayne, PA, USA: 2008. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi. CLSI document M38-A2.

Clinical and Laboratory Standards Institute (CLSI) Approved Standard-Seventh Edition. CLSI; Wayne, PA, USA: 2006. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. CLSI document M7-A7.

Adaptive Synthesis, Supramolecular Behavior, and Biological Properties of Amphiphilic Carbosilane-Phosphonium Dendrons with Tunable Structure

Synthesis and Decontamination Effect on Chemical and Biological Agents of Benzoxonium-Like Salts

The Antibacterial Effects of New N-Alkylpyridinium Salts on Planktonic and Biofilm Bacteria

Wide-Antimicrobial Spectrum of Picolinium Salts