Background: Increasing rates of acquired resistance have justified the critical need for novel antimicrobial drugs. One viable concept is the modification of known drugs. Methods & results: 21 mafenide-based compounds were prepared via condensation reactions and screened for antimicrobial efficacy, which demonstrated promising activity against both Gram-positive and Gram-negative pathogens, pathogenic fungi and mycobacterial strains (minimum inhibitory concentrations from 3.91 μM). Importantly, they retained activity against a panel of superbugs (methicillin- and vancomycin-resistant staphylococci, enterococci, multidrug-resistant Mycobacterium tuberculosis) without any cross-resistance. Unlike mafenide, most of its imines were bactericidal. Toxicity to HepG2 cells was also investigated. Conclusion: Schiff bases were significantly more active than the parent drug, with iodinated salicylidene and 5-nitrofuran/thiophene-methylidene scaffolds being preferred in identifying the most promising drug candidates.
Keywords: Schiff bases; antibacterial activity; antifungal activity; antimycobacterial activity; cytotoxicity; drug resistance; enterococci; imine; mafenide; staphylococci.