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-resistantStaphylococcus aureus(MRSA) andS. aureusATCC 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 compound1fexhibiting 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.

In this study, a series of twenty-two ring-substituted 2-hydroxynaphthalene-1‑carboxanilides were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium marinum, M. kasasii, M. smegmatis. and M. avium paratuberculosis. The compounds were also tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. 2-Hydroxy-N-phenylnaphthalene-1-carboxanilide and 2-hydroxy-N-(3-trifluoromethylphenyl)naphthalene-1-carboxamide (IC₅₀ = 29 µmol/L) were the most active PET inhibitors. Some of tested compounds showed the antibacterial and antimycobacterial activity against the tested strains comparable or higher than the standards ampicillin or isoniazid. Thus, for example, 2-hydroxy-N-(3-nitrophenyl)naphthalene-1-carboxamide showed MIC = 26.0 µmol/L against methicillin-resistant S. aureus and MIC = 51.9 µmol/L against M. marinum, or 2-hydroxy-N-phenylnaphthalene-1-carboxamide demonstrated MIC = 15.2 µmol/L against M. kansasii. The structure-activity relationships for all compounds are discussed.

In this study, a series of twenty-two ring-substituted 3-hydroxy-N-phenylnaphthalene-2-carboxanilides were prepared and characterized. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four Staphylococcus strains and against two mycobacterial species. 3-Hydroxy-N-(2-methoxyphenyl)naphthalene-2-carboxamide showed high biological activity (MIC = 55.0 µmol/L) against S. aureus as well as methicillin-resistant strains. N-(2-Fluorophenyl)-3-hydroxynaphthalene-2-carboxamide showed higher activity (MIC = 28.4 µmol/L) against M. marinum than the standard isoniazid and 3-hydroxy-N-(4-nitrophenyl)naphthalene-2-carboxamide expressed higher activity (MIC = 13.0 µmol/L) against M. kansasii than the standard isoniazid. Cytotoxicity assay of effective antimicrobial compounds was performed using the human monocytic leukemia THP-1 cell line. The PET-inhibiting activity expressed by IC₅₀ value of the most active compound 3-hydroxy-N-(3-nitrophenyl)naphthalene-2-carboxamide was 16.9 μmol/L. The structure-activity relationships of all compounds are discussed.