Title:Synthesis, Antimicrobial Effect and Surface Properties of Hydroxymethylsubstituted Pyridinium Salts
VOLUME: 15 ISSUE: 8
Author(s):Jan Marek, Vera Joskova, Rafael Dolezal, Ondrej Soukup, Marketa Benkova, Alena Fucikova, David Malinak, Vanda Bostikova and Kamil Kuca*
Affiliation:Department of Epidemiology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Department of Biological and Medical Sciences, Faculty of Pharmacy, Charles University, Hradec Kralove, Biomedical Research Centre, University Hospital Hradec Kralove, Hradec Kralove, Biomedical Research Centre, University Hospital Hradec Kralove, Hradec Kralove, Biomedical Research Centre, University Hospital Hradec Kralove, Hradec Kralove, Department of Biology, Faculty of Science, University of Hradec Kralove, Hradec Kralove, Biomedical Research Centre, University Hospital Hradec Kralove, Hradec Kralove, Department of Epidemiology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Department of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove
Keywords:Hydroxymethylpyridinium salts, antimicrobial activity, synthesis, quaternary ammonium salts, critical micelle concentration,
conductivity, cytotoxicity.
Abstract:Background: The cationic surfactants are a huge group of compounds with thousands of
applications. Quaternary Ammonium Salts (QAS) make up the majority of this group. Their countless
applications in chemistry, the food industry and textile industry are indubitable. The antibacterial
and antifungal effect of the various novel QAS is usually referred to in comparison with commercially
used benzalkonium and pyridinium salts, since such compounds have found widespread
use as common disinfectants e.g. in hospitals as prevention against nosocomial infections.
Methods: Three series of N-alkylpyridinium salts with a hydroxymethyl group in positions 2, 3 and
4 were synthesized as novel potential antimicrobial agents. The nucleophilic substitution-type reaction
has been used. The novel compounds have been tested as a disinfection agents against bacteria
and fungi. The microdilution broth method was utilized for antimicrobial evaluation. Conductivity
measurement method has been used for the determination of Critical Micelle Concentration (CMC).
Standard MTT test was used for cytotoxic evaluation.
Results: We have prepared 15 new compounds based on hydroxymethylpyridine in different positions
(2, 3, 4) and the different length of lipophilic alkyl chain on the quaternary nitrogen (C10-18).
The compounds were characterized with analytical data (NMR, HRMS) and tested for in vitro antimicrobial
activity. The highest, and submicromolar antimicrobial activity was achieved for the 3-
hydroxymethylpyridinium salts substituted with longer alkyl chains (C14, C16 and C18). Nhexadecyl-
3-hydroxymethylpyridinium bromide (10b) showed even better performance than standard
benzalkonium salts. Conductometric analysis confirmed the trend of decreasing CMC with
elongation of the alkyl side chain. Generally, the location of the hydroxymethyl function on the
pyridinium scaffold induced only negligible changes in antimicrobial efficacy. Finally, potential use
of the N-alkylhydroxymethylpyridinium salts in practice was supported by MMT tests which
proved relatively low cytotoxicity of the compounds.
Conclusion: We have designed, synthesized and characterized three series of cationic surfactants
based on 2-, 3- and 4-hydroxymethylpyridine. The cationic surfactants differ in the length of alkyl
side-chain (C10, C12, C14, C16, C18). The antimicrobial effect was evaluated against four groups of
microorganisms (gram- positive and gram-negative bacteria, yeasts, and filamentous fungi). The
Critical Micelle Concentrations (CMC) were measured by conductivity method, and finally cytotoxicity
tests were performed.
