This report presents a new modification of the isoniazid (INH) structure linked with different anilines via a carbonyl group obtained by two synthetic procedures and with N-substituted 5-(pyridine-4-yl)-1,3,4-oxadiazole-2-amines prepared by their cyclisation. All synthesised derivatives were characterised by IR, NMR, MS and elemental analyses and were evaluated in vitro for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium avium 330/88, Mycobacterium kansasii 235/80 and one clinical isolated strain of M. kansasii 6509/96. 2-Isonicotinoyl-N-(4-octylphenyl)hydrazinecarboxamide displayed an in vitro efficacy comparable to that of INH for M. tuberculosis with minimum inhibitory concentrations (MICs) of 1-2 μM. Among the halogenated derivatives, the best anti-tuberculosis activity was found for 2-isonicotinoyl-N-(2,4,6-trichlorophenyl)hydrazinecarboxamide (MIC=4 μM). In silico modelling on the enoyl-acyl carrier protein reductase InhA confirmed that longer alkyl substituents are advantageous for the interactions and affinity to InhA. Most of the hydrazinecarboxamides, especially those derived from 4-alkylanilines, exhibited significant activity against INH-resistant nontuberculous mycobacteria.
- MeSH
- aminy chemie MeSH
- aniliny chemie MeSH
- antituberkulotika chemická syntéza farmakologie MeSH
- atypické mykobakteriální infekce mikrobiologie MeSH
- azoly chemie MeSH
- bakteriální léková rezistence MeSH
- bakteriální proteiny antagonisté a inhibitory chemie MeSH
- cyklizace MeSH
- isoniazid analogy a deriváty chemická syntéza farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium avium účinky léků enzymologie růst a vývoj MeSH
- Mycobacterium kansasii účinky léků enzymologie růst a vývoj izolace a purifikace MeSH
- Mycobacterium tuberculosis účinky léků enzymologie růst a vývoj MeSH
- oxidoreduktasy antagonisté a inhibitory chemie MeSH
- pyridiny chemie MeSH
- simulace molekulového dockingu MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
