Improving the antimicrobial activity of old antibacterial drug mafenide: Schiff bases and their bioactivity targeting resistant pathogens

• Published in: Future medicinal chemistry Vol. 15; no. 3; pp. 255 - 274
• Main Authors: Krátký, Martin, Konečná, Klára, Šimková, Adéla, Janďourek, Ondřej, Maixnerová, Jana, Stolaříková, Jiřina, Vejsová, Marcela, Voxová, Barbora, Trejtnar, František, Vinšová, Jarmila
• Format: Journal Article
• Language: English
• Published: England Newlands Press Ltd 01.02.2023
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Infective Agents; antibacterial activity; antifungal activity; antimycobacterial activity; cytotoxicity; drug resistance; enterococci; imine; Mafenide; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Schiff bases; Schiff Bases - pharmacology; staphylococci; antibacterial activity; Schiff bases; mafenide; antimycobacterial activity; imine; staphylococci; drug resistance; antifungal activity; cytotoxicity; enterococci
• ISSN: 1756-8919; 1756-8927
• DOI: 10.4155/fmc-2022-0259

Increasing rates of acquired resistance have justified the critical need for novel antimicrobial drugs. One viable concept is the modification of known drugs. 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 ) without any cross-resistance. Unlike mafenide, most of its imines were bactericidal. Toxicity to HepG2 cells was also investigated. 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.