Naslov
Combating Bacterial Communication With Chloroquine- Based Fumardiamides

Autori
Beus, Maja ; Savijoki, Kirsi ; Patel, Jayendra Z. ; Yli-Kauhaluoma, Jari ; Fallarero, Adyary ; Zorc, Branka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
4th Mini Symposium for Young Scientists of the Section of Medicinal and Pharmaceutical Chemistry / - , 2020, 6-6

Skup
4th Mini Symposium for Young Scientists of the Section of Medicinal and Pharmaceutical Chemistry

Mjesto i datum
Virtualno, online, 08.12.2020

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
quinoline derivatives ; chloroquine ; fumardiamide ; quorum sensing inhibition ; quorum quenching

Sažetak
A cell-to-cell communication, termed quorum sensing (QS), plays a key role in coordinating the biofilm formation and various other pathogenic pathways. By utilizing QS, microbial cells can detect and respond to cell population density and it is considered that molecules or compounds able to interrupt QS pose less selective pressure on the microbes than the conventional antibiotics, thus, contributing less to antibiotic resistance. Strategies that interrupt the QS-communication outside the cell, also called quorum quenching (QQ), are highly promising since the communication system can be blocked without entering the cell. Therefore, search for novel anti-QS compounds preventing the development of specific group behaviour and causing chemical attenuation of biofilm formation is considered the method of choice to combat biofilm infections without boosting the resistance. Quinoline derivatives were shown as effective antagonists of PqsR, the receptor of pqs system of the human pathogen Pseudomonas aeruginosa, which controls the expression of various virulence factors and is involved in the biofilm formation. We have synthesized and tested the activity of four novel fumardiamides with chloroquine (CQ) moiety on one side and scaffolds bearing primary or secondary amino groups on the opposite side of the molecule. For testing anti-QS and bactericidal activities, the C. violaceum ATCC31532 and CV026 strains were used as QS reporters. Our results revealed that compounds 27, 29 and 30 inhibited QS by approx. 46%, which is similar to the activity of quercetin, the positive control for QS (56%), however, the tested compounds showed a negligible bactericidal effect in both strains ranging from 6.5 to 16.2%. Since the compounds had no bactericidal effect on the C. violaceum cells, we considered them as new QQs able to block QS without inducing natural selection pressure as traditional antimicrobial agents. Our results could help in further design of agents targeting cell-to-cell communication and may open new avenues for the combat against drug-resistant bacteria.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Interdisciplinarne prirodne znanosti, Temeljne medicinske znanosti, Farmacija

POVEZANOST RADA