The wide-spectrum antimicrobial effect of novel N-alkyl monoquaternary ammonium salts and their mixtures; the QSAR study against bacteria

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F20%3A50017355" target="_blank" >RIV/62690094:18470/20:50017355 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/20:10417814 RIV/60162694:G44__/20:00556039

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0223523420305560" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0223523420305560</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejmech.2020.112584" target="_blank" >10.1016/j.ejmech.2020.112584</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The wide-spectrum antimicrobial effect of novel N-alkyl monoquaternary ammonium salts and their mixtures; the QSAR study against bacteria

Popis výsledku v původním jazyce

Quaternary ammonium salts (QASs) have been widely used for disinfection purposes because of their low price, high efficacy and low human toxicity for decades. However, precise mechanisms of action nor the powerful versatile agent against all antimicrobial species are known. In this study we have prepared 43 novel N-alkyl monoquaternary ammonium salts including 7 N,N-dialkyl monoquaternary ammonium salts differing bearing alkyl chain either of 12, 14 or 16 carbons. Together with 15 already published QASs we have studied the antimicrobial efficacy of all water-soluble compounds together with standard benzalkonium salts against Gram-positive (G+) and Gram-negative (G-) bacteria, anaerobic spore-forming Cl. difficile, yeasts, filamentous fungi and enveloped Varicella zoster virus (VZV). To address the mechanism of action, lipophilicity seems to be a key parameter which determines antimicrobial efficacy, however, exceptions are likely to occur and therefore QSAR analysis on the efficacy against G+ and G- bacteria was applied. We showed that antibacterial activity is higher when the molecule is larger, more lipophilic, less polar, and contains fewer oxygen atoms, fewer methyl groups bound to heteroatoms or fewer hydrogen atoms bound to polarized carbon atoms. In addition, from an application point of view, we have formulated mixtures, on the basis of obtained efficiency of individual compounds, in order to receive wide-spectrum agent. All formulated mixtures completely eradicated tested G+ and G- strains, including the multidrug-resistant P. aeruginosa as well as in case of yeasts. However, effect on A. fumigatus, Cl. difficile and VZV the exposition towards mixture resulted in significant reduction only. Finally, 3 out of 4 formulated mixtures were safer than reference commercial agent based on benzal-konium salts only in the skin irritation test using reconstructed human epidermidis. (C) 2020 Elsevier Masson SAS. All rights reserved.

Název v anglickém jazyce

The wide-spectrum antimicrobial effect of novel N-alkyl monoquaternary ammonium salts and their mixtures; the QSAR study against bacteria

Popis výsledku anglicky

Quaternary ammonium salts (QASs) have been widely used for disinfection purposes because of their low price, high efficacy and low human toxicity for decades. However, precise mechanisms of action nor the powerful versatile agent against all antimicrobial species are known. In this study we have prepared 43 novel N-alkyl monoquaternary ammonium salts including 7 N,N-dialkyl monoquaternary ammonium salts differing bearing alkyl chain either of 12, 14 or 16 carbons. Together with 15 already published QASs we have studied the antimicrobial efficacy of all water-soluble compounds together with standard benzalkonium salts against Gram-positive (G+) and Gram-negative (G-) bacteria, anaerobic spore-forming Cl. difficile, yeasts, filamentous fungi and enveloped Varicella zoster virus (VZV). To address the mechanism of action, lipophilicity seems to be a key parameter which determines antimicrobial efficacy, however, exceptions are likely to occur and therefore QSAR analysis on the efficacy against G+ and G- bacteria was applied. We showed that antibacterial activity is higher when the molecule is larger, more lipophilic, less polar, and contains fewer oxygen atoms, fewer methyl groups bound to heteroatoms or fewer hydrogen atoms bound to polarized carbon atoms. In addition, from an application point of view, we have formulated mixtures, on the basis of obtained efficiency of individual compounds, in order to receive wide-spectrum agent. All formulated mixtures completely eradicated tested G+ and G- strains, including the multidrug-resistant P. aeruginosa as well as in case of yeasts. However, effect on A. fumigatus, Cl. difficile and VZV the exposition towards mixture resulted in significant reduction only. Finally, 3 out of 4 formulated mixtures were safer than reference commercial agent based on benzal-konium salts only in the skin irritation test using reconstructed human epidermidis. (C) 2020 Elsevier Masson SAS. All rights reserved.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30107 - Medicinal chemistry

Projekt

<a href="/cs/project/NV18-09-00181" target="_blank" >NV18-09-00181: Vývoj polyvalentního dekontaminačního činidla</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

European journal of medicinal chemistry

ISSN

0223-5234

e-ISSN

—

Svazek periodika

206

Číslo periodika v rámci svazku

November

Stát vydavatele periodika

FR - Francouzská republika

Počet stran výsledku

23

Strana od-do

"Article Number: 112584"

Kód UT WoS článku

000579097000004

EID výsledku v databázi Scopus

2-s2.0-85089732498