Reflecting the known biological activity of isoniazid-based hydrazones, seventeen hydrazones of 4-(trifluoromethyl)benzohydrazide as their bioisosters were synthesized from various benzaldehydes and aliphatic ketones. The compounds were screened for their in vitro activity against Mycobacterium tuberculosis, nontuberculous mycobacteria (M. avium, M. kansasii), bacterial and fungal strains. The most antimicrobial potent derivatives were also investigated for their cytostatic and cytotoxic properties against three cell lines. Camphor-based molecule, 4-(trifluoromethyl)-N'-(1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)benzohydrazide, exhibited the highest and selective inhibition of M. tuberculosis with the minimum inhibitory concentration (MIC) of 4 µM, while N'-(4-chlorobenzylidene)-4-(trifluoromethyl)benzohydrazide was found to be superior against M. kansasii (MIC = 16 µM). N'-(5-Chloro-2-hydroxybenzylidene)-4-(trifluoromethyl)benzohydrazide showed the lowest MIC values for gram-positive bacteria including methicillin-resistant Staphylococcus aureus as well as against two fungal strains of Candida glabrata and Trichophyton mentagrophytes within the range of ≤0.49-3.9 µM. The convenient substitution of benzylidene moiety at the position 4 or the presence of 5-chloro-2-hydroxybenzylidene scaffold concomitantly with a sufficient lipophilicity are essential for the noticeable antimicrobial activity. This 5-chlorosalicylidene derivative avoided any cytotoxicity on two mammalian cell cultures (HepG2, BMMΦ) up to the concentration of 100 µM, but it affected the growth of MonoMac6 cells.
- MeSH
- antiinfekční látky chemická syntéza farmakologie toxicita MeSH
- buněčné linie MeSH
- buňky Hep G2 MeSH
- Candida glabrata účinky léků MeSH
- hydrazony chemie farmakologie toxicita MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium avium komplex účinky léků MeSH
- Mycobacterium kansasii účinky léků MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- myši MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The nontuberculous mycobacteria are typically environmental organisms residing in soil and water. These microorganisms can cause a wide range of clinical diseases; pulmonary disease is most frequent, followed by lymphadenitis in children, skin and soft tissue disease, and rare extra pulmonary or disseminated infections. Mycobacterium avium complex is the second most common cause of pulmonary mycobacterioses after M. tuberculosis. This review covers the clinical and laboratory diagnosis of infection caused by the members of this complex and particularities for the treatment of different disease types and patient populations.
- MeSH
- intracelulární infekce bakterií Mycobacterium avium diagnóza etiologie terapie MeSH
- lidé MeSH
- mikrobiologie životního prostředí MeSH
- Mycobacterium avium komplex klasifikace účinky léků genetika MeSH
- rizikové faktory MeSH
- zdroje nemoci mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
A series of new isoniazid hydrazones was synthesized by two procedures. In the first isoniazid was activated with diethoxymethyl acetate and condensed with the appropriate anilines. Alternatively, substituted anilines were activated by diethoxymethyl acetate and subsequently condensed with isoniazid. NMR study confirmed that both synthetic approaches gave the same tautomer. All compounds were screened for in vitro antimycobacterial activity. Most of them exhibited the same activity against Mycobacterium tuberculosis (MIC 1 μmol L(-1)) as isoniazid (INH), better activity against Mycobacterium kansasii 325/80 (MIC 0.125-0.250 μmol L(-1)), high value of selectivity index (SI) and IC(50) between 0.0218 and 0.326 mmol L(-1). Compound 2o with the best SI was used as a model compound for the stability test and was found to be stable at neutral pH, but under acidic conditions it slowly hydrolysed.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- antituberkulotika chemie farmakologie MeSH
- atypické mykobakteriální infekce farmakoterapie MeSH
- buňky Hep G2 MeSH
- hydrazony chemie farmakologie MeSH
- intracelulární infekce bakterií Mycobacterium avium farmakoterapie MeSH
- isoniazid chemie farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium avium komplex účinky léků MeSH
- Mycobacterium kansasii účinky léků MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- tuberkulóza farmakoterapie MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- bakteriální léková rezistence fyziologie MeSH
- dospělí MeSH
- fylogeneze MeSH
- lidé MeSH
- Mycobacterium avium komplex izolace a purifikace účinky léků MeSH
- plicní nemoci mikrobiologie MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus délky restrikčních fragmentů MeSH
- sputum mikrobiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- MeSH
- antibiotická rezistence genetika imunologie účinky léků MeSH
- antituberkulotika * klasifikace terapeutické užití MeSH
- atypické mykobakteriální infekce * diagnóza etiologie terapie MeSH
- hrudní chirurgické výkony * metody využití MeSH
- lidé MeSH
- Mycobacterium avium komplex izolace a purifikace patogenita účinky léků MeSH
- Mycobacterium avium izolace a purifikace patogenita účinky léků MeSH
- Mycobacterium fortuitum izolace a purifikace účinky léků MeSH
- Mycobacterium kansasii izolace a purifikace patogenita účinky léků MeSH
- statistika jako téma MeSH
- Check Tag
- lidé MeSH
