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

Abstract

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 (Pseudomonas quinolone signal)-dependent quorum sensing (QS) of Pseudomonas aeruginosa 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 Chromobacterium violaceum-based reporter, which identified compounds 15–19 and 23 with the highest anti-QS and minimal bactericidal effects in a single experiment. These five compounds were then evaluated against P. aeruginosa PAO1 to assess their ability to prevent biofilm formation, eradicate pre-formed biofilms, and inhibit virulence using pyocyanin as a representative marker. Compound 15 displayed the most potent antibiofilm effect, reducing biofilm formation by nearly 50% and pre-formed biofilm masses by 25%. On the other hand, compound 23 exhibited the most significant antivirulence effect, reducing pyocyanin synthesis by over 70%. Thus, our study highlights the potential of 1,3,4-oxadiazoles 15 and 23 as promising scaffolds to combat P. aeruginosa. Additionally, interactive QS systems should be considered to achieve maximal anti-QS activity against this clinically relevant species.

Twinning Organosuperelasticity in a 4-Nitroanthranilic Acid Solvate Crystal

“…The development of pharmaceutical substances is aided using anthranilic acid derivatives as a precursor in the synthesis of nonsteroidal anti-inflammatory drugs (NSAIDs). They also serve as an essential precursor to produce Pseudomonas quinolone signal (PQS), and its halogenated derivatives have been found to be inhibitors of PQS biosynthesis. , In addition, 4-nitroanthranilic acid exhibits mutagenic characteristics, connecting it to the mutagenicity seen in plant extracts. This substance demonstrates how diversified it is by acting as a key building block for pharmaceuticals, a key component in bacterial signaling pathways, and a potential target for mutagenesis studies …”

Synthesis of 2-Amino-N′-aroyl(het)arylhydrazides, DNA Photocleavage, Molecular Docking and Cytotoxicity Studies against Melanoma CarB Cell Lines

“…The attachment of Anthranilic acid DACHZs (AA DACHZs, Figure 2, G, H) bear an additional functional amine group which contributes to their chemistry, biology and technology. Derivatives such as G may give rise to 1,3,4-oxadiazoles [7][8][9][10], 1,2,3-benzotriazine-4-ones [11], 3-amido-1,2dihydro substituted quinazolinones [12][13][14][15][16][17], 3-amido substituted quinazolinones [10,18], quinazolinone containing fused polycyclic compounds [19,20] or N-N axially chiral 3,3 ′bisquinazolinones [21]. Furthermore, their well-positioned electron-donating atoms allow metal complexation which, depending on the metal and the conditions applied, range from the formation of simple metal complexes [22][23][24] to the important metal-organic macrocycles (MOMs) [25,26] with Mn, Ga and In [27][28][29].…”