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.
- MeSH
- ampicilin farmakologie MeSH
- anilidy chemická syntéza farmakologie MeSH
- antibakteriální látky chemická syntéza farmakologie MeSH
- buněčné linie MeSH
- chloroplasty účinky léků fyziologie MeSH
- fotosyntéza účinky léků fyziologie MeSH
- lidé MeSH
- methicilin rezistentní Staphylococcus aureus účinky léků růst a vývoj MeSH
- mikrobiální testy citlivosti MeSH
- mikrobiální viabilita účinky léků MeSH
- monocyty cytologie účinky léků MeSH
- Mycobacterium avium subsp. paratuberculosis účinky léků růst a vývoj MeSH
- Mycobacterium tuberculosis účinky léků růst a vývoj MeSH
- naftaleny chemická syntéza farmakologie MeSH
- rifampin farmakologie MeSH
- Spinacia oleracea účinky léků fyziologie MeSH
- transport elektronů účinky léků fyziologie MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Mycobacterium avium subsp. paratuberculosis (MAP) has a high degree of resistance to chemical and physical procedures frequently used for the elimination of other bacteria. Recently, a method for the determination of viability by exposure of MAP to propidium monoazide (PMA) and subsequent real time quantitative PCR (qPCR) was established and found to be comparable with culture. The aim of this study was to apply the PMA qPCR method to determine the impact of increasing concentration or time and repeated cycles of the application of selected disinfectants on MAP viability. Different MAP isolates responded to the same type of stress in different ways. The laboratory strain CAPM 6381 had the highest tolerance, while the 8819 low-passage field isolate was the most sensitive. Ultraviolet exposure caused only a partial reduction in MAP viability; all MAP isolates were relatively resistant to chlorine. Only the application of peracetic acid led to the total elimination of MAP. Repeated application of the treatments resulted in more significant decreases in MAP viability compared to single increases in the concentration or time of exposure to the disinfectant.
- MeSH
- azidy * MeSH
- bakteriální proteiny genetika metabolismus MeSH
- chlor farmakologie MeSH
- dezinficiencia farmakologie MeSH
- kvantitativní polymerázová řetězová reakce veterinární MeSH
- kyselina peroctová farmakologie MeSH
- mikrobiální viabilita účinky léků MeSH
- Mycobacterium avium subsp. paratuberculosis účinky léků MeSH
- propidium analogy a deriváty MeSH
- ultrafialové záření MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A series of twenty substituted 2-hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(alkoxycarbonyl)amino]benzoates were prepared and characterized. As similar compounds have been described as potential antimycobacterials, primary in vitro screening of the synthesized carbamates was also performed against two mycobacterial species. 2-Hydroxy-3-[2-(2,6-dimethoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, 2-hydroxy-3-[2-(4-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, and 2-hydroxy-3-[2-(2-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride showed higher activity against M. avium subsp. paratuberculosis and M. intracellulare than the standards ciprofloxacin, isoniazid, or pyrazinamide. Cytotoxicity assay of effective compounds was performed using the human monocytic leukaemia THP-1 cell line. Compounds with predicted amphiphilic properties were also tested for their effects on the rate of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. All butyl derivatives significantly stimulated the rate of PET, indicating that the compounds can induce conformational changes in thylakoid membranes resulting in an increase of their permeability and so causing uncoupling of phosphorylation from electron transport.
- MeSH
- antibakteriální látky chemická syntéza farmakologie MeSH
- benzoáty chemická syntéza farmakologie MeSH
- karbamáty chemická syntéza farmakologie MeSH
- Mycobacterium avium subsp. paratuberculosis účinky léků MeSH
- rozpřahující látky chemická syntéza farmakologie MeSH
- Spinacia oleracea účinky léků MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of paratuberculosis in ruminants, has a lipid-rich cell wall which facilitates its survival and persistence in the environment. This property of the organism is exploited when it is cultured as decontaminating agents and antibiotics are used to suppress the growth of contaminating microflora, but such treatments can also negatively affect the isolation of MAP itself. The objective of this study was to assess the effect of the 'VAN' antibiotics (vancomycin, amphotericin B and nalidixic acid) on the viability of MAP using a propidium monoazide real time quantitative PCR (PMA qPCR) and culture. Long-term (5 week) treatment with VAN antibiotics resulted in a larger decrease in bacterial numbers compared to short-term (3 day) exposure. The PMA qPCR assay indicated that 50 μg/mL of vancomycin, 50 μg/mL of nalidixic acid, and 200 μg/mL of amphotericin B were 'threshold' concentrations, respectively, above which the decline in the viability of MAP was statistically significant. Using culture, these threshold concentrations were 100 μg/mL of vancomycin, 50-100 μg/mL of nalidixic acid, and 100 μg/mL of amphotericin B, respectively. Given that the two methods were found to be comparable, the PMA qPCR is a potentially more convenient and effective alternative to culture in detecting MAP.
- MeSH
- amfotericin B farmakologie MeSH
- antibakteriální látky farmakologie MeSH
- azidy metabolismus MeSH
- časové faktory MeSH
- kvantitativní polymerázová řetězová reakce metody MeSH
- kyselina nalidixová farmakologie MeSH
- Mycobacterium avium subsp. paratuberculosis účinky léků růst a vývoj izolace a purifikace metabolismus MeSH
- paratuberkulóza diagnóza mikrobiologie MeSH
- počet mikrobiálních kolonií metody MeSH
- přežvýkavci mikrobiologie MeSH
- propidium analogy a deriváty metabolismus MeSH
- vankomycin farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
