Synthesis and antimycobacterial evaluation of pyrazinamide derivatives with benzylamino substitution
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
23237840
DOI
10.1016/j.bmcl.2012.11.052
PII: S0960-894X(12)01504-1
Knihovny.cz E-resources
- MeSH
- Antitubercular Agents chemical synthesis pharmacology MeSH
- Benzylamines chemistry MeSH
- Inhibitory Concentration 50 MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Molecular Structure MeSH
- Mycobacterium drug effects MeSH
- Pyrazinamide chemical synthesis pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antitubercular Agents MeSH
- Benzylamines MeSH
- Pyrazinamide MeSH
A series of 19 new compounds related to pyrazinamide were synthesized, characterized with analytical data and screened for in vitro whole cell antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium kansasii and two types of Mycobacterium avium. The series consisted of 3-(benzylamino)-5-cyanopyrazine-2-carboxamides and 3-(benzylamino)pyrazine-2,5-dicarbonitriles with various substituents on the phenyl ring. RP-HPLC method was used to determine the lipophilicity of the prepared compounds. Nine compounds exerted similar or better activity against Mycobacterium tuberculosis compared to pyrazinamide (MIC=6.25-12.5 μg/mL). 3-(Benzylamino)pyrazine-2,5-dicarbonitrile inhibited all of the tested mycobacterial strains with MIC within the range 12.5-25 μg/mL. Although not the most active, 4-NH(2) substituted compounds possessed the lowest in vitro cytotoxicity (hepatotoxicity), leading to selectivity index SI=5.5 and SI >21.
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