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Ring-substituted 8-hydroxyquinoline-2-carboxanilides as potential antimycobacterial agents
Jiri Kos1, Iveta Zadrazilova1, Eoghan Nevin2
1Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1/3, 612 42 Brno, Czech Republic.
Bioorganic & Medicinal Chemistry
|July 18, 2015
Summary
New 8-hydroxyquinoline-2-carboxanilides show potent antimycobacterial activity, particularly against Mycobacterium avium subsp. paratuberculosis. Some compounds exhibit activity superior to rifampicin with minimal cytotoxicity.
Area of Science:
- Medicinal Chemistry
- Microbiology
- Pharmacology
Background:
- Tuberculosis and non-tuberculous mycobacterial infections pose significant global health challenges.
- There is a continuous need for novel antimycobacterial agents with improved efficacy and safety profiles.
- 8-Hydroxyquinoline derivatives have shown promise as antimicrobial agents.
Purpose of the Study:
- To synthesize and characterize a series of novel ring-substituted 8-hydroxyquinoline-2-carboxanilides.
- To evaluate the in vitro antimycobacterial activity of these compounds against key mycobacterial species.
- To assess the cytotoxicity of the synthesized compounds.
Main Methods:
- Synthesis and characterization of twenty-two 8-hydroxyquinoline-2-carboxanilides.
- In vitro antimicrobial screening against Mycobacterium tuberculosis H37Ra, Mycobacterium avium complex, and M. avium subsp. paratuberculosis.
- Minimum Inhibitory Concentration (MIC) determination.
- MTT assay for assessing mycobacterial cell metabolism.
- Cytotoxicity screening using THP-1 cells.
Main Results:
- Several synthesized compounds demonstrated significant antimycobacterial activity against M. avium subsp. paratuberculosis, with some exceeding rifampicin's potency.
- Compounds like 8-hydroxy-N-[3-(trifluoromethyl)phenyl]- and 8-hydroxy-N-[4-(trifluoromethyl)phenyl]quinoline-2-carboxamide exhibited MICs of 24 μM against all tested strains.
- Derivatives containing methoxyphenyl, methylphenyl, bromophenyl, and trifluoromethylphenyl groups showed promising activity against M. tuberculosis and M. avium subsp. paratuberculosis.
- MTT assays indicated a significant reduction in M. tuberculosis H37Ra cell metabolism.
- No significant cytotoxicity was observed for the compounds up to 30 μM concentration in THP-1 cells.
Conclusions:
- The synthesized 8-hydroxyquinoline-2-carboxanilides represent a promising class of compounds for antimycobacterial drug development.
- Specific derivatives show potent activity against M. avium subsp. paratuberculosis, warranting further investigation.
- The compounds exhibit a favorable safety profile with low cytotoxicity, suggesting potential for therapeutic application.
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