To develop new potential antimycobacterial drugs, a series of pyrazinamide derivatives was designed, synthesized and tested for their ability to inhibit the growth of selected mycobacterial strains (Mycobacterium tuberculosis H37Rv, Mycobacterium kansasii and two strains of Mycobacterium avium). This Letter is focused on binuclear pyrazinamide analogues containing the -CONH-CH2- bridge, namely on N-benzyl-5-chloropyrazine-2-carboxamides with various substituents on the phenyl ring and their comparison with some analogously substituted 5-chloro-N-phenylpyrazine-2-carboxamides. Compounds from the N-benzyl series exerted lower antimycobacterial activity against M. tuberculosis H37Rv then corresponding anilides, however comparable with pyrazinamide (12.5-25 μg/mL). Remarkably, 5-chloro-N-(4-methylbenzyl)pyrazine-2-carboxamide (8, MIC=3.13 μg/mL) and 5-chloro-N-(2-chlorobenzyl)pyrazine-2-carboxamide (1, MIC=6.25 μg/mL) were active against M. kansasii, which is naturally unsusceptible to PZA. Basic structure-activity relationships are presented.
- MeSH
- Amides chemical synthesis pharmacology MeSH
- Anti-Bacterial Agents chemical synthesis pharmacology MeSH
- Antitubercular Agents chemical synthesis pharmacology MeSH
- Mycobacterium tuberculosis drug effects MeSH
- Pyrazines chemical synthesis pharmacology MeSH
- Structure-Activity Relationship MeSH
- Publication type
- Letter MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Amides MeSH
- Anti-Bacterial Agents MeSH
- Antitubercular Agents MeSH
- Pyrazines MeSH
