Phenanthrolinic analogs of quinolones show antibacterial activity against M. tuberculosis

Several phenanthrolinic analogs of quinolones have been synthesized and their antibacterial activity tested against Mycobacterium tuberculosis, other mycobacterial species and bacteria from other genera. Some of them show high activity (of the range observed for rifampicin) against M. tuberculosis r...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2020-12, Vol.207, p.112821, Article 112821
Main Authors: Coulibaly, Songuigama, Cimino, Mena, Ouattara, Mahama, Lecoutey, Cédric, Buchieri, Maria V., Alonso-Rodriguez, Noelia, Briffotaux, Julien, Mornico, Damien, Gicquel, Brigitte, Rochais, Christophe, Dallemagne, Patrick
Format: Article
Language:English
Subjects:
Antitubercular Agents
Antitubercular Agents - chemistry
Antitubercular Agents - pharmacology
Dihydrophenanthrolinones
Drug Design
Drug Resistance, Bacterial
Drug Resistance, Bacterial - drug effects
Fluoroquinolones
Life Sciences
Microbial Sensitivity Tests
Mycobacterium tuberculosis
Mycobacterium tuberculosis - drug effects
Phenanthrolines
Phenanthrolines - chemistry
Quinolones
Quinolones - chemistry
Quinolones - pharmacology
Tuberculosis
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Summary:Several phenanthrolinic analogs of quinolones have been synthesized and their antibacterial activity tested against Mycobacterium tuberculosis, other mycobacterial species and bacteria from other genera. Some of them show high activity (of the range observed for rifampicin) against M. tuberculosis replicating in vitro and in vivo (infected macrophages) conditions. These derivatives show the same activity with all or several M. tuberculosis complex bacterial mutants resistant to fluoroquinolones (FQ). This opens the way to the construction of new drugs for the treatment of FQ resistant bacterial infections, including tuberculosis. Several compounds showed also activity against Staphylococcus aureus and probably other species. These compounds do not show major toxicity. We conclude that the novel phenanthrolinic derivatives described here are potent hits for further developments of new antibiotics against bacterial infectious diseases including tuberculosis in particular those resistant to FQ. [Display omitted] •Phenanthrolinic analogs of fluoroquinolones retains their antituberculosis activity.•The antituberculosis activity is clear in replication condition inside macrophages.•Activity is maintained against bacterial mutants resistant to fluoroquinolones.•No significant toxicity is observed with the most promising compounds.•Mechanism of action seems to target Mycobacterium tuberculosis DNA gyrase.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2020.112821