Synthesis and broad-spectrum biocidal effect of novel gemini quaternary ammonium compounds

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F25%3A00563517" target="_blank" >RIV/60162694:G44__/25:00563517 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/24:10483790 RIV/00216275:25310/24:39922213 RIV/00179906:_____/24:10483790

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0045206824005510?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0045206824005510?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.bioorg.2024.107646" target="_blank" >10.1016/j.bioorg.2024.107646</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Synthesis and broad-spectrum biocidal effect of novel gemini quaternary ammonium compounds

Popis výsledku v původním jazyce

Since the discovery of antimicrobial agents, the misuse of antibiotics has led to the emergence of bacterial strains resistant to both antibiotics and common disinfectants like quaternary ammonium compounds (QACs). A new class, 'gemini' QACs, which contain two polar heads, has shown promise. Octenidine (OCT), a representative of this group, is effective against resistant microorganisms but has limitations such as low solubility and high cytotoxicity. In this study, we developed 16 novel OCT derivatives. These compounds were subjected to in silico screening to predict their membrane permeation. Testing against nosocomial bacterial strains (G+ and G-) and their biofilms revealed that most compounds were highly effective against G+ bacteria, while compounds 7, 8, and 10-12 were effective against G-bacteria. Notably, compounds 6-8 were significantly more effective than OCT and BAC standards across the bacterial panel. Compound 12 stood out due to its low cytotoxicity and broadspectrum antimicrobial activity, comparable to OCT. It also demonstrated impressive antifungal activity. Compound 1 was highly selective to fungi and four times more effective than OCT without its cytotoxicity. Several compounds, including 4, 6, 8, 9, 10, and 12, showed strong virucidal activity against murine cytomegalovirus and herpes simplex virus 1. In conclusion, these gemini QACs, especially compound 12, offer a promising alternative to current disinfectants, addressing emerging resistances with their enhanced antimicrobial, antifungal, and virucidal properties.

Název v anglickém jazyce

Synthesis and broad-spectrum biocidal effect of novel gemini quaternary ammonium compounds

Popis výsledku anglicky

Since the discovery of antimicrobial agents, the misuse of antibiotics has led to the emergence of bacterial strains resistant to both antibiotics and common disinfectants like quaternary ammonium compounds (QACs). A new class, 'gemini' QACs, which contain two polar heads, has shown promise. Octenidine (OCT), a representative of this group, is effective against resistant microorganisms but has limitations such as low solubility and high cytotoxicity. In this study, we developed 16 novel OCT derivatives. These compounds were subjected to in silico screening to predict their membrane permeation. Testing against nosocomial bacterial strains (G+ and G-) and their biofilms revealed that most compounds were highly effective against G+ bacteria, while compounds 7, 8, and 10-12 were effective against G-bacteria. Notably, compounds 6-8 were significantly more effective than OCT and BAC standards across the bacterial panel. Compound 12 stood out due to its low cytotoxicity and broadspectrum antimicrobial activity, comparable to OCT. It also demonstrated impressive antifungal activity. Compound 1 was highly selective to fungi and four times more effective than OCT without its cytotoxicity. Several compounds, including 4, 6, 8, 9, 10, and 12, showed strong virucidal activity against murine cytomegalovirus and herpes simplex virus 1. In conclusion, these gemini QACs, especially compound 12, offer a promising alternative to current disinfectants, addressing emerging resistances with their enhanced antimicrobial, antifungal, and virucidal properties.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/NU23-09-00334" target="_blank" >NU23-09-00334: Vývoj širokospektrých dezinfekčních látek se zesílenou virucidní aktivitou</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Bioorganic Chemistry

ISSN

0045-2068

e-ISSN

1090-2120

Svazek periodika

151

Číslo periodika v rámci svazku

Oct

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

107646

Kód UT WoS článku

001275301800001

EID výsledku v databázi Scopus

2-s2.0-85198992245