Synthesis, Antimicrobial Effect and Surface Properties of Hydroxymethyl-substituted Pyridinium Salts

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F18%3A50014452" target="_blank" >RIV/62690094:18470/18:50014452 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60162694:G44__/18:43889545 RIV/00216208:11160/18:10376436 RIV/00179906:_____/18:10376436

Výsledek na webu

<a href="http://dx.doi.org/10.2174/1570180814666171110142233" target="_blank" >http://dx.doi.org/10.2174/1570180814666171110142233</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.2174/1570180814666171110142233" target="_blank" >10.2174/1570180814666171110142233</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis, Antimicrobial Effect and Surface Properties of Hydroxymethyl-substituted Pyridinium Salts

Popis výsledku v původním jazyce

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 (C-14, C-16 and C-18). N-hexadecyl- 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 (C-10, C-12, C-14, C-16, C-18). 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.

Název v anglickém jazyce

Synthesis, Antimicrobial Effect and Surface Properties of Hydroxymethyl-substituted Pyridinium Salts

Popis výsledku anglicky

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 (C-14, C-16 and C-18). N-hexadecyl- 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 (C-10, C-12, C-14, C-16, C-18). 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

<a href="/cs/project/NV15-31847A" target="_blank" >NV15-31847A: Vývoj nových dezinfekčních činidel proti patogenům vyskytujících se v nemocničním prostředí</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Letters in drug design &amp; discovery

ISSN

1570-1808

e-ISSN

—

Svazek periodika

15

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

AE - Spojené arabské emiráty

Počet stran výsledku

15

Strana od-do

828-842

Kód UT WoS článku

000436085100003

EID výsledku v databázi Scopus

—