Aminobenzylated 4-Nitrophenols as Antibacterial Agents Obtained from 5-Nitrosalicylaldehyde through a Petasis Borono–Mannich Reaction

[Image: see text] Multidrug-resistant bacteria are one of the current biggest threats to public health and are responsible for most nosocomial infections. Herein, we report the efficient and facile synthesis of antibacterial agents aminoalkylphenols, derived from 5-nitrosalicyladehyde and prepared through a Petasis borono–Mannich multicomponent reaction. Minimum inhibitory concentrations (MICs) as low as 1.23 μM for a chlorine derivative were determined for multidrug-resistant Gram-positive bacteria, namely, Staphylococcus aureus and Enterococcus faecalis, two of the main pathogens responsible for infections in a hospital environment. The most promising antibacterial agents were further tested against eight strains of four Gram-positive species in order to elucidate their antibacterial broadness. In vitro cytotoxicity assays of the most active aminoalkylphenol revealed considerably lower toxicity against mammalian cells, as concentrations one order of magnitude higher than the determined MICs were required to induce human keratinocyte cell death. The phenol moiety was verified to be important in deeming the antibacterial properties of the analyzed compounds, although no correlation between such properties and their antioxidant activity was observed. A density functional theory computational study substantiated the ability of aminoalkylphenols to serve as precursors of ortho-quinone methides.