Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Ivana Perković
* ,
Tanja Poljak
,
Kirsi Savijoki
* ORCID logo ,
Pekka Varmanen
ORCID logo ,
Gordana Maravić-Vlahoviček
ORCID logo ,
Maja Beus
,
Anja Kučević
,
Ivan Džajić
,
Zrinka Rajić
ORCID logo
Version 1 : Received: 10 July 2023 / Approved: 11 July 2023 / Online: 12 July 2023 (21:25:14 CEST)

A peer-reviewed article of this Preprint also exists.

Perković, I.; Poljak, T.; Savijoki, K.; Varmanen, P.; Maravić-Vlahoviček, G.; Beus, M.; Kučević, A.; Džajić, I.; Rajić, Z. Synthesis and Biological Evaluation of New Quinoline and Anthranilic Acid Derivatives as Potential Quorum Sensing Inhibitors. Molecules 2023, 28, 5866. Perković, I.; Poljak, T.; Savijoki, K.; Varmanen, P.; Maravić-Vlahoviček, G.; Beus, M.; Kučević, A.; Džajić, I.; Rajić, Z. Synthesis and Biological Evaluation of New Quinoline and Anthranilic Acid Derivatives as Potential Quorum Sensing Inhibitors. Molecules 2023, 28, 5866.

Abstract

Inhibition of quorum sensing (QS)-dependent biofilm formation and virulence is extensively investigated as a novel approach to combat bacterial pathogens by impeding their ability to cause antibiotic-tolerant diseases. Such strategies are considered a promising alternative to conventional antibacterial therapy since interrupting the central cell-to-cell communication system imposes less selective pressure on the target pathogen. In this study, novel hybrid compounds composed of anthranilic acids substituted with halogens at different positions of the phenyl ring, and 4-(2-aminoethyl/4-aminobuthyl)amino-7-chloroquinoline linked via 1,3,4-oxadiazole were synthesized using standard procedures. Their anti-QS activities were evaluated using Chromobacterium violaceum ATCC31532 (anti-biofilm and bactericidal activities) and Pseudomonas aeruginosa PAO1 (anti-biofilm/-virulence activities). The results showed that compounds 15–19 and 23 inhibited the production of violacein, the QS-inducible pigment, in C. violaceum to a similar extent as the model QS inhibitor - quercetin (83.5–90%). Compound 15 exhibited the strongest effect on P. aeruginosa in the anti-biofilm screening, reducing its ability to form biofilm by almost 50%, while compounds 16 and 19 were able to reduce the biofilm formation by approximately 30%. However, compound 23 did not demonstrate significant anti-biofilm activity and only inhibited pyocyanin production in P. aeruginosa. In conclusion, this study suggests that 1,3,4-oxadiazoles 15, 16, and 19 are the most promising compounds for future research as novel QS inhibitors against Gram-negative bacteria equipped with different QS signaling pathways.

Keywords

4-amino-7-chloroquinoline; 1,3,4-oxadiazole; anthranilic acid; synthesis; quorum sensing; anti-biofilm; P. aeruginosa; PQS

Subject

Medicine and Pharmacology, Pharmacy

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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