Design, green synthesis, and quorum sensing quenching potential of novel 2-oxo-pyridines containing a thiophene/furan scaffold and targeting a LasR gene on P. aeruginosa

Abstract

New 2-oxo-pyridines containing thiophene/furan scaffold targeting LasR gene on P. aeruginosa using green synthesis approach.

Small Schiff Base Molecules—A Possible Strategy to Combat Biofilm-Related Infections

“…Combining 6-amino-4-(thiophen-2-yl)-2-oxo-pyridine-3,5-dicarbonitrile (18) and 6amino-4-(furan-2-yl)-2-oxo-pyridine-3,5-dicarbonitrile (19) with aromatic aldehydes and ketones, two series of antimicrobial Schiff bases (18a-c and 19a-c) were synthesized under both conventional and green conditions (ceric ammonium nitrate catalysis) [109]. Biological screening revealed significant antimicrobial potential for azomethines, especially on Gram-negatives, surpassing or equalizing references (gentamicin and fluconazole) and biocidal modes of action.…”

“…Structure-activity relationships revealed that azomethine is important for activity, which varied according to the substituents in position one (imine groups) and four (furanyl, thiophenyl) on pyridine moiety (Figure 6). Benzylidene and 1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene increased the antibacterial spectrum, with electron-donating groups (hydroxy, ethoxy, bromo) being beneficial for MRSA and E. coli biofilm inhibition [109]. P. aeruginosa uses two QS systems, las and rhl, that rely on transcriptional activators (LasR and RhlR, respectively) and autoinducer molecules (N-3-oxo-dodecanoyl-Lhomoserine lactone, respectively N-butyryl-L-homoserine lactone) [143].…”

“…Structure-activity relationships revealed that azomethine is important for activity, which varied according to the substituents in position one (imine groups) and four (furanyl, thiophenyl) on pyridine moiety (Figure 6). Benzylidene and 1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene increased the antibacterial spectrum, with electron-donating groups (hydroxy, ethoxy, bromo) being beneficial for MRSA and E. coli biofilm inhibition [109]. 4-Amino-3-mercapto-6-(trifluoromethyl)-1,2,4-triazin-5(4H)-one was used as the starting point for the synthesis of six Schiff bases (20a-f) [110].…”

“…aeruginosa uses two QS systems, las and rhl, that rely on transcriptional activators (LasR and RhlR, respectively) and autoinducer molecules (N-3-oxo-dodecanoyl-Lhomoserine lactone, respectively N-butyryl-L-homoserine lactone)[143]. Interfering with these systems may serve as a strategy to reduce virulence and pathogenicity[144].Combining 6-amino-4-(thiophen-2-yl)-2-oxo-pyridine-3,5-dicarbonitrile (18) and 6amino-4-(furan-2-yl)-2-oxo-pyridine-3,5-dicarbonitrile(19) with aromatic aldehydes and ketones, two series of antimicrobial Schiff bases (18a-c and 19a-c) were synthesized under both conventional and green conditions (ceric ammonium nitrate catalysis)[109]. Biological screening revealed significant antimicrobial potential for azomethines, especially on Gram-negatives, surpassing or equalizing references (gentamicin and fluconazole) and biocidal modes of action.…”

Chitosan–Aspirin Combination Inhibits Quorum-Sensing Synthases (lasI and rhlI) in Pseudomonas aeruginosa

“…By binding to and interacting with rhlR in the rhl TCS, the autoinducer C4-HSL increases RhlI expression and triggers the controlled synthesis of cytotoxic lectins, rhamnolipids, lasB elastase, and Life 2024, 14, 481 2 of 13 pyocyanin, all of which are essential for virulence and the formation and development of biofilms. The QS systems Las, Rhl, Pqs, and Iqs are interconnected hierarchically [4,5].…”