A New Kind of Quinonic-Antibiotic Useful Against Multidrug-Resistant S. aureus and E. faecium Infections

Indexación: Scopus.A rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics and reducing the therapeutic arsenal available for treatment of infectious diseases. In the present study, we developed a new class of compounds with antibacterial activity obtained by a simple, two step synthesis and screened the products for in vitro antibacterial activity against ATCC® strains using the broth microdilution method. The compounds exhibited minimum inhibitory concentrations (MIC) of 1⁻32 μg/mL against Gram-positive ATCC® strains. The structure⁻activity relationship indicated that the thiophenol ring is essential for antibacterial activity and the substituents on the thiophenol ring module, for antibacterial activity. The most promising compounds detected by screening were tested against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) clinical isolates. We found remarkable activity against VREF for compounds 7 and 16, were the MIC50/90 were 2/4 µg/mL and 4/4 µg/mL, respectively, while for vancomycin the MIC50/90 was 256/512 µg/mL. Neither compound affected cell viability in any of the mammalian cell lines at any of the concentrations tested. These in vitro data show that compounds 7 and 16 have an interesting potential to be developed as new antibacterial drugs against infections caused by VREF.https://www.mdpi.com/1420-3049/23/7/177

Free radical formation and characterization of nitroanisole isomer reduction in different media

A comprehensive study of the electrochemical characteristics of 2-, 3-, and 4-nitroanisole isomers in three different electrolytic media has been carried out. Furthermore, kinetic characterization of the one-electron reduction product from these isomers in these media is also reported. Also, free radicals were characterized in aprotic media by electron paramagnetic resonance through their corresponding hyperfine splitting constants. In protic media (30% ethanol/0.1 M Britton-Robinson buffer pH 2- 12) 2-, and 3- nitroanisole isomers gave an irreversible well-defined peak over the entire pH range on Hg in a reaction involving four electrons to give the hydroxylamine derivative. However, in the case of 4-nitroanisole the kinetic characterization of the corresponding nitro radical anion was successfully achieved in this medium at pH 10.5, exhibiting a k(2disp) value of 19,000 (M s)(-1). In this medium the ease of reduction at pH 7 was 2-nitroanisole (2-NA). 3-nitroanisole (3-NA). 4-nitroanisole (4-NA). In mixed aqueous-organic media [0.015 M aqueous citrate dimethylformamide (DMF): 60: 40, 0.3 M KCl, and 0.1 M tetrabutylammonium iodide (TBAI) at pH greater than or equal to 10.5 the isolation of the couple by cyclic voltammetry and the electrochemical characterization of the nitro radical anion corresponding to the three compounds were achieved. Calculated disproportionation second-order rate constants, k(2disp), had an average value of 10,900 +/- 930 (M s)(-1), 2400 +/- 400 (M s)(-1), and 5000 +/- 600 (M s)(-1) for 2-NA, 3-NA, and 4-NA, respectively. Also, the reactivity of the radicals toward glutathione was quantitatively assessed through the calculation of the respective apparent interaction rate constants. In aprotic media (0.1 M TBAI in DMF) the nitro radical anions were more stable than in the mixed media, with the following second-order decay rate constant, k(2dim), values: 1100 +/- 100 (M s)(-1), 1600 +/- 150 (M s)(-1), and 650 +/- 70 (M s)(-1) for 2-NA, 3-NA, and 4-NA, respectively