A series of nine substituted 2-hydroxy-N-[1-oxo-1-(phenylamino)alkan-2-yl]benzamides was assessed as prospective bactericidal agents against three clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus ATCC 29213 as the reference and quality control strain. The minimum bactericidal concentration was determined by subculturing aliquots from MIC determination onto substance-free agar plates. The bactericidal kinetics of compounds 5-chloro-2-hydroxy-N-[(2S)-3-methyl-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino}butan-2-yl]benzamide (1f), N-{(2S)-1-[(4-bromophenyl)amino]-3-methyl-1-oxobutan-2-yl}-4-chloro-2-hydroxybenzamide (1g), and 4-chloro-N-{(2S)-1-[(3,4-dichlorophenyl)amino]-3-methyl-1-oxobutan-2-yl}-2-hydroxybenzamide (1h) was established by time-kill assay with a final concentration of the compound equal to 1x, 2x, and 4x MIC; aliquots were removed at 0, 4, 6, 8, and 24 h time points. The most potent bactericidal agent was compound 1f exhibiting remarkable rapid concentration-dependent bactericidal effect even at 2x MIC at 4, 6, and 8 h (with a reduction in bacterial count ranging from 3.08 to 3.75 log10 CFU/mL) and at 4x MIC at 4, 6, 8, and 24 h (5.30 log10 CFU/mL reduction in bacterial count) after incubation against MRSA 63718. Reliable bactericidal effect against other strains was maintained at 4x MIC at 24 h.

Department of Chemical Drugs Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Brno Palackeho 1 3 612 42 Brno Czech Republic

Department of Chemical Drugs Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Brno Palackeho 1 3 612 42 Brno Czech Republic ; Department of Infectious Diseases and Microbiology Faculty of Veterinary Medicine University of Veterinary and Pharmaceutical Sciences Brno Palackeho 1 3 612 42 Brno Czech Republic ; CEITEC VFU University of Veterinary and Pharmaceutical Sciences Brno Palackeho 1 3 612 42 Brno Czech Republic

Department of Infectious Diseases and Microbiology Faculty of Veterinary Medicine University of Veterinary and Pharmaceutical Sciences Brno Palackeho 1 3 612 42 Brno Czech Republic

Department of Infectious Diseases and Microbiology Faculty of Veterinary Medicine University of Veterinary and Pharmaceutical Sciences Brno Palackeho 1 3 612 42 Brno Czech Republic ; CEITEC VFU University of Veterinary and Pharmaceutical Sciences Brno Palackeho 1 3 612 42 Brno Czech Republic

Department of Inorganic and Organic Chemistry Faculty of Pharmacy in Hradec Kralove Charles University Prague Heyrovskeho 1203 500 05 Hradec Kralove Czech Republic

Institute of Organic Chemistry and Technology Faculty of Chemical Technology University of Pardubice Studentska 573 532 10 Pardubice Czech Republic

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