Naslov
Amidoquinuclidine salts with potent activity against Listeria monocytogenes

Autori
Crnčević, Doris ; Sabljić, Antonio ; Krce, Lucija ; Primožič, Ines ; Odžak, Renata ; Šprung, Matilda

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
International Symposium on Medicinal Chemistry

Mjesto i datum
Nica, Francuska, 04.09.2022. - 08.09.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Podatak o recenziji nije dostupan

Ključne riječi
Quaternary ammonium salts ; quinuclidine ; antimicrobial activity ; mechanism of action

Sažetak
Listeriosis is a serious disease caused by food contaminated with Listeria monocytogenes. This bacterium is found in soil and surface water samples, but can also be found in dairy products, meat and seafood. Membrane-active antimicrobials such as quaternary ammonium salts (QASs), represent an important class of bacteriostatic and biocidal amphiphilic agents that are widely used in daily life. Given the widespread use of QASs, there have been reports of L. monocyogenes isolates resistant to these compounds. Here, we present the synthesis of a new series of quaternary amidoquinuclidine salts with potent antibacterial activity against L. monocytogenes. The antibacterial activity was determined for bacteria in the form of suspension and biofilm in the low micromolar range. The newly synthesized 3- aminoquinuclidines (C10, C12, C14, and C16) were quaternized with allyl or methyl substituents. We found that regardless of the type of substituent, the derivatives with longer alkyl chains had minimal inhibitory concentrations against L. monocytogenes that were almost identical to those of the standards (BAB, CPC, and cefotaxime). The identified candidates had low toxicity to healthy human cell lines with potent genotoxic activity against bacterial cells. In addition to the mechanism of action, we demonstrated that these agents target the cell membrane and cause membrane perforation and cell death. Parallel artificial membrane permeability assays mimicking human skin showed that candidates with longer alkyl chains did not penetrate the membrane, highlighting their potential application as disinfectants against this and other highly pathogenic bacteria.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA