Naslov
Synthesis and biological evaluation of quinoline and anthranilic acid derivatives as potential quorum sensing inhibitors

Autori
Perković, Ivana ; Poljak, Tanja ; Beus, Maja ; Savijoki, Kirsi ; Varmanen, Peka ; Kučević, Anja ; Džajić, Ivan

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

Izvornik
9th BBBB International Conference on Pharmaceutical Sciences Pharma Sciences of Tomorrow: Book of Abstracts / Obreza, Aleš ; Dreu, Rok ; Zvonar Pobirk, Alenka ; Sterle Zorec, Barbara - Ljubljana : Slovensko farmacevtsko društvo in Univerza v Ljubljani, Fakulteta za farmacijo, 2022, 89-90

ISBN
978-961-94230-4-2

Skup
9th BBBB International Conference on Pharmaceutical Sciences Pharma: Sciences of Tomorrow

Mjesto i datum
Ljubljana, Slovenija, 15.09.2022. - 17.09.2022

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
quorum sensing, synthesis, quinoline, anthranilic acid, hybrids

Sažetak
Quorum sensing (QS) is a mechanism of bacterial cell-to-cell communication and gene expression co- ordination ; an important strategy performed by bacteria to enhance its virulence and promote host damage [1]. Thus, inhibition of QS is widely investigated as a novel approach to combat bacteria which would act by blocking their ability to cause disease and is considered as an alternative approach to conventional antibacterial therapy [2]. In the present study, we report the synthesis of novel compounds composed of two distinctive structural motifs, anthranilic acid and 4-amino-7-chloroquinoline derivatives linked with oxadiazole or semicarbazide. The compounds were screened for their anti-QS and antibacterial activity using gram-negative Chromobacterium violaceum as the reporter strain. A series of oxadiazole linked compounds composed of anthranilic acid and 7-chloro-quinoline moieties were synthesized together with their precursors. The 4-amino-7-chloroquinoline part of the molecule varied in the length of the alkyl chain on the 4- aminoquinoline group (2 or 4 carbon atoms) and anthranilic acid was substituted at various positions of the phenyl ring with halogen atoms (F, Cl or Br). The compounds were obtained by using standard synthetic procedures. The 1, 3, 4- oxadiazole and semicarbazide derivatives were screened for their anti QS and bactericidal activity. Quercetin (Q) was used as the positive control for QS and azithromycin as the positive control for bactericidal activity (cell viability). Inhibitory activity was tested at 400 μM concentrations and for the most potent compounds at 100 μM and 40 μM as well. Six out of total of twelve tested compounds inhibited the violacein production in C. violaceum to the same extent as Q. However, two compounds exerted also a strong bactericidal effect on the reporter. Dose- concentration-response analyses with the most promising compounds indicated that each compound with concentrations at 400 and 100 μM reduced the violacein production by more than 50 % compared to the control cells with DMSO, while the viability of the reporter under the same conditions was marginally affected.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Farmacija

POVEZANOST RADA