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

含有噻吩/呋喃支架并靶向铜绿假单胞菌 Las R 基因的新型 2-氧代吡啶的设计、绿色合成和群体感应猝灭潜力

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作者:Yousry A Ammar, Ahmed Ragab, M A Migahed, S Al-Sharbasy, Mohamed A Salem, Omnia Karem M Riad, Heba Mohammed Refat M Selim, Gehad A Abd-Elmaksoud, Moustafa S Abusaif

Methods

a green approach using CAN and a conventional method. The structure of designed derivatives was confirmed using different spectroscopies (IR and 1H/13C NMR) and elemental analysis. The designed derivatives exhibited good to moderate inhibition zones against bacterial and fungal pathogens. In addition, six compounds 2a,b, 3a,b, and 6a,b displayed potency against tested pathogens with eligible MIC and MBC values compared to standard antimicrobial agents. Compound 2a displayed MIC values of 15.6 μg mL-1 compared to Gentamicin (MIC = 250 μg mL-1 against K. pneumoniae), while compound 6b exhibited super-potent activity against P. aeruginosa, and K. pneumoniae with MIC values of 62.5 and 125 μg mL-1, as well as MBC values of 31.25 and 15.6 μg mL-1 compared to Gentamicin (MIC = 250 and 125 μg mL-1 and MBC = 62.5 μg mL-1), respectively. Surprisingly, these six derivatives revealed bactericidal and fungicidal potency and remarkable anti-biofilm activity that could significantly reduce the biofilm formation against MRSA, E. coli, P. aeruginosa, and C. albicans. Furthermore, the most active derivatives reduced the LasR gene's production between 10-40% at 1/8 MICs compared with untreated P. aeruginosa. Besides, they demonstrated promising safety profile on Vero cells (normal cell lines) with IC50 values ranging between (175.17 ± 3.49 to 344.27 ± 3.81 μg mL-1). In addition, the in silico ADMET prediction was carried out and the

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