Synthesis and Biological Evaluation of New Quinoline and Anthranilic Acid Derivatives as Potential Quorum Sensing Inhibitors

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 15; p. 5866
• Main Authors: Perković, Ivana, Poljak, Tanja, Savijoki, Kirsi, Varmanen, Pekka, Maravić-Vlahoviček, Gordana, Beus, Maja, Kučević, Anja, Džajić, Ivan, Rajić, Zrinka
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.08.2023; MDPI
• Subjects: 1,3,4-oxadiazole; 4-amino-7-chloroquinoline; Acids; Analysis; anthranilic acid; Antibacterial agents; antibiofilm/virulence; Antibiotics; Antimicrobial agents; Bacteria; Bacterial infections; Biofilms; Biosynthesis; Carbon; Cystic fibrosis; Drug resistance in microorganisms; Pathogens; Quinoline; quorum sensing; synthesis; Virulence; Virulence (Microbiology); Germany; synthesis; Chromobacterium violaceum; PQS; quorum sensing; anthranilic acid; 1,3,4-oxadiazole; 4-amino-7-chloroquinoline; Pseudomonas aeruginosa; antibiofilm/virulence
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28155866

Inhibiting quorum sensing (QS), a central communication system, is a promising strategy to combat bacterial pathogens without antibiotics. Here, we designed novel hybrid compounds targeting the PQS ( quinolone signal)-dependent quorum sensing (QS) of that is one of the multidrug-resistant and highly virulent pathogens with urgent need of new antibacterial strategies. We synthesized 12 compounds using standard procedures to combine halogen-substituted anthranilic acids with 4-(2-aminoethyl/4-aminobuthyl)amino-7-chloroquinoline, linked via 1,3,4-oxadiazole. Their antibiofilm activities were first pre-screened using Gram-negative -based reporter, which identified compounds - and with the highest anti-QS and minimal bactericidal effects in a single experiment. These five compounds were then evaluated against PAO1 to assess their ability to prevent biofilm formation, eradicate pre-formed biofilms, and inhibit virulence using pyocyanin as a representative marker. Compound displayed the most potent antibiofilm effect, reducing biofilm formation by nearly 50% and pre-formed biofilm masses by 25%. On the other hand, compound exhibited the most significant antivirulence effect, reducing pyocyanin synthesis by over 70%. Thus, our study highlights the potential of 1,3,4-oxadiazoles and as promising scaffolds to combat . Additionally, interactive QS systems should be considered to achieve maximal anti-QS activity against this clinically relevant species.