Synthesis and Antimicrobial Evaluation of 6-Alkylamino-N-phenylpyrazine-2-carboxamides
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25676890
DOI
10.1111/cbdd.12536
Knihovny.cz E-resources
- Keywords
- antibacterial evaluation, antimycobacterial evaluation, cytotoxicity, multidrug-resistant strains, pyrazinamide derivatives,
- MeSH
- Antifungal Agents chemistry pharmacology MeSH
- Anti-Infective Agents chemical synthesis chemistry pharmacology MeSH
- Antitubercular Agents chemical synthesis chemistry pharmacology MeSH
- Cell Line drug effects MeSH
- Humans MeSH
- Methicillin-Resistant Staphylococcus aureus drug effects MeSH
- Microbial Sensitivity Tests MeSH
- Mycobacterium tuberculosis drug effects MeSH
- Drug Evaluation, Preclinical methods MeSH
- Molecular Docking Simulation MeSH
- Chemistry Techniques, Synthetic MeSH
- Structure-Activity Relationship MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antifungal Agents MeSH
- Anti-Infective Agents MeSH
- Antitubercular Agents MeSH
This work presents synthesis and antimicrobial evaluation of nineteen 6-alkylamino-N-phenylpyrazine-2-carboxamides. Antimycobacterial activity was determined against Mycobacterium tuberculosis H37Rv, M. kansasii and two strains of M. avium. Generally, the antimycobacterial activity increased with prolongation of simple alkyl chain and culminated in compounds with heptylamino substitution (3e, 4e) with MIC = 5-10 μm against M. tuberculosis H37Rv. On the contrary, derivatives with modified alkyl chain (containing e.g. terminal methoxy or hydroxy group) as well as phenylalkylamino derivatives were mainly inactive. The most active compounds (with hexyl to octylamino substitution) were evaluated for their in vitro activity against drug-resistant strains of M. tuberculosis and possessed activity comparable to that of the reference drug isoniazid. None of the tested compounds were active against M. avium. Some derivatives exhibited activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (best MIC = 7.8 μm), while Gram-negative strains as well as tested fungal strains were completely unsusceptible. Active compounds were tested for in vitro toxicity on various cell lines and in most cases were non-toxic up to 100 μm.
References provided by Crossref.org
Design, Synthesis and Evaluation of N-pyrazinylbenzamides as Potential Antimycobacterial Agents
