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1.
J Med Chem ; 66(21): 14735-14754, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37874867

RESUMO

Pseudomonas aeruginosa (P. aeruginosa) is well-known to cause biofilm-associated drug resistance and infections that often lead to treatment failure. Herein, we reported a dual-acting antibiofilm strategy by inhibiting both the bacterial quorum sensing system and the iron uptake system. A series of coumarin derivatives were synthesized and evaluated, and compound 4t was identified as the most effective biofilm inhibitor (IC50 = 3.6 µM). Further mechanistic studies have confirmed that 4t not only inhibits the QS systems but also competes strongly with pyoverdine as an iron chelator, causing an iron deficiency in P. aeruginosa. Additionally, 4t significantly improved the synergistic antibacterial effects of ciprofloxacin and tobramycin by more than 200-1000-fold compared to the single-dose antibiotic treatments. Therefore, our study has shown that 4t is a potentially novel antibacterial synergist candidate to treat bacterial infections.


Assuntos
Pseudomonas aeruginosa , Percepção de Quorum , Cumarínicos/farmacologia , Antibacterianos/farmacologia , Biofilmes , Ferro/farmacologia , Homeostase , Fatores de Virulência , Proteínas de Bactérias
2.
J Hazard Mater ; 449: 130994, 2023 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-36821898

RESUMO

Microplastics (MPs) usually coexist with heavy metals (HMs) in soil. MPs can influence HMs mobility and bioavailability, but the underlying mechanisms remain largely unexplored. Here, polyethylene and polypropylene MPs were selected to investigate their effects and mechanisms of sorption-desorption, bioaccessibility and bioavailability of cadmium (Cd) in paddy soil. Batch experiments indicated that MPs significantly reduced the Cd sorption in soil (p < 0.05). Accordingly, soil with the MPs had lower boundary diffusion constant of Cd (C1= 0.847∼1.020) and the Freundlich sorption constant (KF = 0.444-0.616) than that without the MPs (C1 = 0.894∼1.035, KF = 0.500-0.655). X-ray diffraction, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy analyses suggested that the MPs reduced Cd chemisorption, by covering the soil active sites and thus blocking complexation of Cd with active oxygen sites and interrupting the formation of CdCO3 and Cd3P2 precipitates. Such effects of MPs enhanced about 1.2-1.5 times of Cd bioaccessibility and bioavailability in soil. Almost the same effects but different mechanisms of polyethylene and polypropylene MPs on Cd sorption in the soil indicated the complexity and pervasiveness of their effects. The findings provide new insights into impacts of MPs on the fate and risk of HMs in agricultural soil.


Assuntos
Metais Pesados , Poluentes do Solo , Microplásticos/química , Cádmio/química , Plásticos/química , Solo , Polietileno/química , Polipropilenos , Disponibilidade Biológica , Adsorção , Poluentes do Solo/análise
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