Naslov
Discovery of novel quaternary ammonium compounds based on quinuclidine-3-ol as new potential antimicrobial candidates

Autori
Bazina, Linda ; Maravić, Ana ; Krce, Lucija ; Soldo, Barbara ; Odžak, Renata ; Bučević Popović, Viljemka ; Aviani, Ivica ; Primožič, Ines ; Šprung, Matilda

Izvornik
European journal of medicinal chemistry (0223-5234) 163 (2019); 626-635

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
quaternary ammonium compounds ; antimicrobial activity ; quinuclidine ; cytotoxicity

Sažetak
Quaternary ammonium compounds (QACs) are amphiphilic molecules displaying a broad-spectrum of antibacterial activity. QACs are commonly used antiseptics in industrial, home and hospital settings. Given the emergence of the QAC-resistant bacteria, there is an urgent need to design new QACs with good antimicrobial activity, able to escape the host resistance mechanism. Therefore, a series of QACs derived from quinuclidine-3-ol and an alkyl chain of variable length (QOH-C3 to -C14), was designed and synthesized. The antimicrobial potential of the new monoquaternary QACs was surveyed against seventeen strains of emerging food spoilage and pathogenic microorganisms, including clinical multidrug-resistant ESKAPE isolates. The QOH-C14 proved to have the strongest antimicrobial activity. It was highly active against all pathogens tested, particularly against the Gram-positive bacteria with minimal inhibitory concentrations (MICs) ranging from 0.06 to 3.9 µg/mL, and fungi exerting the MIC90 between 0.12 and 3.9 µg/mL. The potency of QOH-C14, confirmed that alkyl chains are an important part of the structure with their lengths playing a critical role in bioactivity of these compounds. The atomic force microscopy images show the disruption of a cell membrane upon the treatment with QOH-C14. These results were additionally confirmed by flow cytometry and fluorescence microscopy. A relatively low toxicity toward healthy human cells underline that QOH-C14 has a potential as new QAC antimicrobial candidate.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA