RESUMO
Antimicrobial resistance (AMR) is fast becoming a medical crisis affecting the entire global population. World Health Organization (WHO) statistics show that globally 0.7 million people are dying yearly due to the emergence of AMR. By 2050, the expected number of lives lost will be 10 million per year. Acinetobacter baumannii is a dreadful nosocomial pathogen that has developed multidrug resistance (MDR) to several currently prescribed antibiotics worldwide. Overexpression of drug efflux transporters (DETs) is one of the mechanisms of multidrug resistance (MDR) in Acinetobacter baumannii. Therefore, blocking the DET can raise the efficacy of the existing antibiotics by increasing their residence time inside the bacteria. In silico screening of five synthetic compounds against three drug efflux pump from A. baumannii has identified KSA5, a novel imidazo[4,5-g]quinoline-4,9-dione derivative, to block the efflux of antibiotics. Molecular docking and simulation results showed that KSA5 could bind to adeB, adeG, and adeJ by consistently interacting with ligand-binding site residues. KSA5 has a higher binding free energy and a lower HOMO-LUMO energy gap than PAßN, suggesting a better ability to interact and inhibit DETs. Further analysis showed that KSA5 is a drug-like molecule with optimal physicochemical and ADME properties. Hence, KSA5 could be combined with antibiotics to overcome antimicrobial resistance.Communicated by Ramaswamy H. Sarma.
RESUMO
As an alternate for the conventional glass-based pH sensor which is associated with problems like fragile nature, alkaline error, and potential drift, the development of a new redox-sensitive pH probe-modified electrode that could show potential, current-drift and surface-fouling free voltammetric pH sensing is a demanding research interest, recently. Herein, we report a substituted carbazole-quinone (Car-HQ) based new redox-active pH-sensitive probe that contains benzyl and bromo-substituents, immobilized multiwalled carbon nanotube modified glassy carbon (GCE/MWCNT@Car-HQ) and screen-printed three-in-one (SPE/MWCNT@Car-HQ) electrodes for selective, surface-fouling free pH sensor application. This new system showed a well-defined surface-confined redox peak at an apparent standard electrode potential, Eo' = - 0.160 V versus Ag/AgCl with surface-excess value, Γ = 47 n mol cm-2 in pH 7 phosphate buffer solution. When tested with various electroactive chemicals and biochemicals such as cysteine, hydrazine, NADH, uric acid, and ascorbic acid, MWCNT@Car-HQ showed an unaltered redox-peak potential and current values without mediated oxidation/reduction behavior unlike the conventional hydroquinone, anthraquinone and other redox mediators based voltammetry sensors with serious electrocatalytic effects and in turn potential and current drifts. A strong π-π interaction, nitrogen-atom assisted surface orientation and C-C bond formation on the graphitic structure of MWCNT are the plausible reasons for stable and selective voltammetric pH sensing application of MWCNT@Car-HQ system. Using a programed/in-built three-in-one screen printed compatible potentiostat system, voltammetric pH sensing of 3 µL sample of urine, saliva, and orange juice samples with pH values comparable to that of milliliter volume-based pH-glass electrode measurements has been demonstrated.
