A series of fifteen new N-alkoxyphenylanilides of 3-hydroxynaphthalene-2-carboxylic acid was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Staphylococcus aureus, three methicillin-resistant S. aureus strains, Mycobacterium tuberculosis H37Ra and M. avium subsp. paratuberculosis. Some of the tested compounds showed antibacterial and antimycobacterial activity against the tested strains comparable with or higher than that of the standards ampicillin or rifampicin. 3-Hydroxy-N-(2-propoxyphenyl)naphthalene-2-carboxamide and N-[2-(but-2-yloxy)-phenyl]-3-hydroxynaphthalene-2-carboxamide had MIC = 12 µM against all methicillin-resistant S. aureus strains; thus their activity is 4-fold higher than that of ampicillin. The second mentioned compound as well as 3-hydroxy-N-[3-(prop-2-yloxy)phenyl]-naphthalene-2-carboxamide had MICs = 23 µM and 24 µM against M. tuberculosis respectively. N-[2-(But-2-yloxy)phenyl]-3-hydroxynaphthalene-2-carboxamide demonstrated higher activity against M. avium subsp. paratuberculosis than rifampicin. Screening of the cytotoxicity of the most effective antimycobacterial compounds was performed using THP-1 cells, and no significant lethal effect was observed for the most potent compounds. The compounds were additionally tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. N-(3-Ethoxyphenyl)-3-hydroxynaphthalene-2-carboxamide (IC50 = 4.5 µM) was the most active PET inhibitor. The structure-activity relationships are discussed.

• Keywords
• hydroxynaphthalene-2-carboxanilides, in vitro antibacterial activity, in vitro antimycobacterial activity, in vitro cytotoxicity, photosynthetic electron transport inhibition, structure-activity relationships,
• MeSH
• Ampicillin pharmacology   MeSH
• Anilides chemical synthesis   pharmacology   MeSH
• Anti-Bacterial Agents chemical synthesis   pharmacology   MeSH
• Cell Line MeSH
• Chloroplasts drug effects   physiology   MeSH
• Photosynthesis drug effects   physiology   MeSH
• Humans MeSH
• Methicillin-Resistant Staphylococcus aureus drug effects   growth & development   MeSH
• Microbial Sensitivity Tests MeSH
• Microbial Viability drug effects   MeSH
• Monocytes cytology   drug effects   MeSH
• Mycobacterium avium subsp. paratuberculosis drug effects   growth & development   MeSH
• Mycobacterium tuberculosis drug effects   growth & development   MeSH
• Naphthalenes chemical synthesis   pharmacology   MeSH
• Rifampin pharmacology   MeSH
• Spinacia oleracea drug effects   physiology   MeSH
• Electron Transport drug effects   physiology   MeSH
• Cell Survival drug effects   MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Ampicillin MeSH
• Anilides MeSH
• Anti-Bacterial Agents MeSH
• Naphthalenes MeSH
• Rifampin MeSH

In this work a series of 15 N-benzylamine substituted 5-amino-6-methyl-pyrazine-2,3-dicarbonitriles was prepared by the aminodehalogenation reactions using microwave assisted synthesis with experimentally set and proven conditions. This approach for the aminodehalogenation reaction was chosen due to its higher yields and shorter reaction times. The products of this reaction were characterized by IR, NMR and other analytical data. The compounds were evaluated for their antibacterial, antifungal and herbicidal activity. Compounds 3 (R=3,4-Cl), 9 (R=2-Cl) and 11 (R=4-CF3) showed good antimycobacterial activity against Mycobacterium tuberculosis (MIC=6.25 µg/mL). It was found that the lipophilicity is important for antimycobacterial activity and the best substitution on the benzyl moiety of the compounds is a halogen or trifluoromethyl group according to Craig's plot. The activities against bacteria or fungi were insignificant. The presented compounds also inhibited photosynthetic electron transport in spinach chloroplasts and the IC50 values of the active compounds varied in the range from 16.4 to 487.0 µmol/L. The most active substances were 2 (R=3-CF3), 3 (R=3,4-Cl) and 11 (R=4-CF3). A linear dependence between lipophilicity and herbicidal activity was observed.

• MeSH
• Antitubercular Agents chemical synthesis   pharmacology   MeSH
• Chloroplasts drug effects   metabolism   MeSH
• Photosynthesis drug effects   MeSH
• Halogenation MeSH
• Herbicides chemical synthesis   pharmacology   MeSH
• Inhibitory Concentration 50 MeSH
• Microbial Sensitivity Tests MeSH
• Microwaves MeSH
• Mycobacterium smegmatis drug effects   MeSH
• Mycobacterium tuberculosis drug effects   MeSH
• Nitriles chemical synthesis   pharmacology   MeSH
• Pyrazines chemical synthesis   pharmacology   MeSH
• Spinacia oleracea drug effects   metabolism   MeSH
• Electron Transport drug effects   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antitubercular Agents MeSH
• Herbicides MeSH
• Nitriles MeSH
• Pyrazines MeSH