In this study, a series of twenty-two ring-substituted 8-hydroxyquinoline-2-carboxanilides was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, Mycobacterium avium complex and M. avium subsp. paratuberculosis. Some of the tested compounds showed the antimycobacterial activity against M. avium subsp. paratuberculosis comparable with or higher than that of rifampicin. 8-Hydroxy-N-[3-(trifluoromethyl)phenyl]- and 8-hydroxy-N-[4-(trifluoromethyl)phenyl]quinoline-2-carboxamide showed MIC=24 μM against all tested mycobacterial strains. 3-Methoxyphenyl- and 3-methylphenyl derivatives expressed MIC=27 or 29 μM also against all the tested strains. Their activity against M. avium subsp. paratuberculosis was 4-fold higher than that of rifampicin. 2-Bromophenyl- and 2-(trifluoromethyl)phenyl derivatives had MIC=23 or 24 μM against M. tuberculosis. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT assay. Screening of cytotoxicity of the compounds was performed using the THP-1 cells, and no significant lethal effect was observed up to tested concentration 30 μM. The structure-activity relationships are discussed.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- buněčné linie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium avium účinky léků MeSH
- Mycobacterium tuberculosis účinky léků metabolismus MeSH
- oxychinolin chemie MeSH
- preklinické hodnocení léčiv metody MeSH
- testy toxicity MeSH
- vztahy mezi strukturou a aktivitou * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In this study, a series of twenty-two ring-substituted 6-hydroxynaphthalene-2-carboxanilides was prepared and characterized. Primary in vitro screening of the synthesized compounds was performed against Mycobacterium tuberculosis H37Ra, Mycobacterium avium complex and M. avium subsp. paratuberculosis. Derivatives substituted by trifluoromethyl, bromo, methyl and methoxy moieties in C'(3) and C'(4) positions of the anilide ring showed 2-fold higher activity against M. tuberculosis than isoniazid and 4.5-fold higher activity against M. avium subsp. paratuberculosis than rifampicin. 6-Hydroxy-N-(2-methylphenyl)naphthalene-2-carboxamide had MIC=29 μM against M. avium complex. A significant decrease of mycobacterial cell metabolism (viability of M. tuberculosis H37Ra) was observed using MTT assay. Screening of the cytotoxicity of the most effective antimycobacterial compounds was performed using the THP-1 cells, and no significant lethal effect was observed. The structure-activity relationships are discussed.
- MeSH
- anilidy chemická syntéza chemie farmakologie MeSH
- antibakteriální látky chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- Mycobacterium cytologie účinky léků MeSH
- nádorové buněčné linie MeSH
- naftoly chemická syntéza chemie farmakologie MeSH
- proliferace buněk účinky léků MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH