Series of thirteen 1-[(2-chlorophenyl)carbamoyl]naphthalen-2-yl carbamates and thirteen 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl carbamates with alkyl/cycloalkyl/arylalkyl chains were prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, two methicillin-resistant S. aureus strains, Mycobacterium marinum, and M. kansasii. 1-[(2-Chlorophenyl)carbamoyl]naphthalen-2-yl ethylcarbamate and 1-[(2-nitrophenyl)carbamoyl]naphthalen-2-yl ethylcarbamate showed antistaphylococcal (MICs = 42 µM against MRSA) and antimycobacterial (MICs = 21 µM) activity against the tested strains comparable with or higher than that of the standards ampicillin and isoniazid. In the case of bulkier carbamate tails (R > propyl/isopropyl), the activity was similar (MICs ca. 70 µM). Screening of the cytotoxicity of both of the most effective compounds was performed using THP-1 cells, and no significant lethal effect was observed (LD50 >30 µM). The structure-activity relationships are discussed.

• Keywords
• carbamates, hydroxynaphthalene-carboxamides, in vitro antibacterial activity, in vitro antimycobacterial activity, in vitro cytotoxicity assay, structure-activity relationships,
• MeSH
• Anti-Infective Agents * chemical synthesis   chemistry   pharmacology   MeSH
• Cytotoxins * chemical synthesis   chemistry   pharmacology   MeSH
• Carbamates * chemical synthesis   chemistry   pharmacology   MeSH
• Humans MeSH
• Methicillin-Resistant Staphylococcus aureus growth & development   MeSH
• Mycobacterium tuberculosis growth & development   MeSH
• Cell Line, Tumor MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Infective Agents * MeSH
• Cytotoxins * MeSH
• Carbamates * MeSH

The development of novel antimicrobial agents represents a timely research topic. Eighteen salicylanilide 4-(trifluoromethyl)benzoates were evaluated against Mycobacterium tuberculosis, M. avium and M. kansasii, eight bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA) and for the inhibition of mycobacterial isocitrate lyase. Some compounds were further screened against drug-resistant M. tuberculosis and for their cytotoxicity. Minimum inhibitory concentrations (MICs) for all mycobacterial strains were within 0.5-32 μmol/L, with 4-chloro-2-[4-(trifluoromethyl)phenylcarbamoyl]phenyl 4-(trifluoromethyl)benzoate superiority. Gram-positive bacteria including MRSA were inhibited with MICs ³ 0.49 μmol/L, while Gram-negative ones were much less susceptible. Salicylanilide 4-(trifluoromethyl)benzoates showed significant antibacterial properties, for many strains being comparable to standard drugs (isoniazid, benzylpenicillin) with no cross-resistance. All esters showed mild inhibition of mycobacterial isocitrate lyase and four compounds were comparable to 3-nitropropionic acid without a direct correlation between in vitro MICs and enzyme inhibition.

• MeSH
• Anti-Bacterial Agents pharmacology   MeSH
• Benzoates pharmacology   MeSH
• Nitro Compounds pharmacology   MeSH
• Isocitrate Lyase antagonists & inhibitors   metabolism   MeSH
• Methicillin-Resistant Staphylococcus aureus drug effects   MeSH
• Microbial Sensitivity Tests MeSH
• Mycobacterium avium drug effects   MeSH
• Mycobacterium kansasii drug effects   MeSH
• Mycobacterium tuberculosis drug effects   MeSH
• Propionates pharmacology   MeSH
• Salicylanilides pharmacology   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 3-nitropropionic acid MeSH Browser
• Anti-Bacterial Agents MeSH
• Benzoates MeSH
• Nitro Compounds MeSH
• Isocitrate Lyase MeSH
• Propionates MeSH
• salicylanilide MeSH Browser
• Salicylanilides MeSH