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

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.