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1.
Ann Clin Microbiol Antimicrob ; 23(1): 60, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965559

RESUMO

BACKGROUND: Gram-negative bacteria (GNB) are becoming increasingly resistant to a wide variety of antibiotics. There are currently limited treatments for GNB, and the combination of antibiotics with complementary mechanisms has been reported to be a feasible strategy for treating GNB infection. The inability to cross the GNB outer membrane (OM) is an important reason that a broad spectrum of Gram-positive only class of antibiotics (GPOAs) is lacking. Polymyxins may help GPOAs to permeate by disrupting OM of GNB. OBJECTIVE: To identify what kind of GPOAs can be aided to broaden their anti-GNB spectrum by polymyxins, we systematically investigated the synergy of eight GPOAs in combination with colistin (COL) and polymyxin B (PMB) against GNB in vitro. METHODS: The synergistic effect of COL or PMB and GPOAs combinations against GNB reference strains and clinical isolates were determined by checkerboard tests. The killing kinetics of the combinations were assessed using time-kill assays. RESULTS: In the checkerboard tests, polymyxins-GPOAs combinations exert synergistic effects characterized by species and strain specificity. The synergistic interactions on P. aeruginosa strains are significantly lower than those on strains of A. baumannii, K. pneumoniae and E. coli. Among all the combinations, COL has shown the best synergistic effect in combination with dalbavancin (DAL) or oritavancin (ORI) versus almost all of the strains tested, with FICIs from 0.16 to 0.50 and 0.13 to < 0.28, respectively. In addition, the time-kill assays demonstrated that COL/DAL and COL/ORI had sustained bactericidal activity. CONCLUSIONS: Our results indicated that polymyxins could help GPOAs to permeate the OM of specific GNB, thus showed synergistic effects and bactericidal effects in the in vitro assays. In vivo combination studies should be further conducted to validate the results of this study.


Assuntos
Antibacterianos , Colistina , Sinergismo Farmacológico , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Polimixina B , Polimixinas , Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Polimixinas/farmacologia , Polimixina B/farmacologia , Humanos , Colistina/farmacologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos
2.
Chem Sci ; 15(21): 8156-8162, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38817557

RESUMO

The first straightforward strategy for the synthesis of 1,4-dicarbonyl Z-alkenes has been developed via an electrochemical cross-coupling reaction of sulfoxonium ylides and alkynes with water. The metal-free protocol showed an easy-to-handle nature, good functional group tolerance, and high Z-stereoselectivity, which is rare in previous cases. The proposed reaction mechanism was convincingly established by carrying out a series of control experiments, cyclic voltammetry experiments, and density functional theory (DFT) studies.

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