Synthesis and Biological Evaluation of N-Alkoxyphenyl-3-hydroxynaphthalene-2-carboxanilides

Molecules. 2015 May 27;20(6):9767-87. doi: 10.3390/molecules20069767.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ampicillin / pharmacology
  • Anilides / chemical synthesis
  • Anilides / pharmacology*
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Chloroplasts / drug effects
  • Chloroplasts / physiology
  • Electron Transport / drug effects
  • Electron Transport / physiology
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Methicillin-Resistant Staphylococcus aureus / growth & development
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Monocytes / cytology
  • Monocytes / drug effects
  • Mycobacterium avium subsp. paratuberculosis / drug effects
  • Mycobacterium avium subsp. paratuberculosis / growth & development
  • Mycobacterium tuberculosis / drug effects
  • Mycobacterium tuberculosis / growth & development
  • Naphthalenes / chemical synthesis
  • Naphthalenes / pharmacology*
  • Photosynthesis / drug effects
  • Photosynthesis / physiology
  • Rifampin / pharmacology
  • Spinacia oleracea / drug effects
  • Spinacia oleracea / physiology
  • Structure-Activity Relationship


  • Anilides
  • Anti-Bacterial Agents
  • Naphthalenes
  • Ampicillin
  • Rifampin