Sulfonamide-salicylaldehyde imines active against methicillin- and trimethoprim/sulfonamide-resistant Staphylococci

• Published in: Future medicinal chemistry Vol. 13; no. 22; pp. 1945 - 1962
• Main Authors: Krátký, Martin, Konečná, Klára, Janoušek, Jiří, Janďourek, Ondřej, Maixnerová, Jana, Kalivodová, Sára, Trejtnar, František, Vinšová, Jarmila
• Format: Journal Article
• Language: English
• Published: England 01.11.2021
• Subjects: Aldehydes - chemistry; Aldehydes - pharmacology; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Drug Resistance, Bacterial - drug effects; Imines - chemistry; Imines - pharmacology; Microbial Sensitivity Tests; Molecular Structure; Staphylococcus - drug effects; Sulfonamides - chemistry; Sulfonamides - pharmacology; antibacterial activity; Schiff bases; imine; sulfamethoxazole; sulfonamides; drug resistance; in vitro activity; Staphylococcus aureus; cytotoxicity
• ISSN: 1756-8919; 1756-8927
• DOI: 10.4155/fmc-2021-0169

Increasing resistance has resulted in an urgent need for new antimicrobial drugs. A systematic me-too approach was chosen to modify clinically used sulfonamides to obtain their imines. Twenty-five compounds were synthesized and evaluated for their antibacterial activity. The most active compounds were also investigated against methicillin- and trimethoprim/sulfamethoxazole (SMX)-resistant Gram-positive species. shared the highest susceptibility including resistant strains with minimum inhibitory concentrations from 3.91 μM (≥2.39 μg ml ). Crucially, the compounds inhibit MRSA and trimethoprim/SMX-resistant without any cross-resistance. Modification of parent sulfonamides turned a bacteriostatic effect into a bactericidal effect. Toxicity for HepG2 and hemolytic properties were also determined. The presence of a dihalogenated salicylidene moiety is required for optimal activity. Based on toxicity, promising derivatives for further investigation were identified.