Straightforward palladium-mediated synthesis and biological evaluation of benzo[j]phenanthridine-7,12-diones as anti-tuberculosis agents
| Autor: | Luc Verschaeve, Sven Claessens, Roel Anthonissen, Tuyen Nguyen Van, Davie Cappoen, Maryse Fauville, Kris Huygen, Thorbjorg Einarsdottir, Norbert De Kimpe, Jan Jacobs, Gaston Stanislas Marcell Diels |
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| Rok vydání: | 2011 |
| Předmět: |
Magnetic Resonance Spectroscopy
medicine.drug_class Cell Survival Antibiotics Antitubercular Agents Drug resistance Microbial Sensitivity Tests Mass Spectrometry Microbiology Cell Line Mycobacterium tuberculosis chemistry.chemical_compound Inhibitory Concentration 50 Mice Drug Discovery Spectroscopy Fourier Transform Infrared medicine Animals Humans Cytotoxicity Pathogen Pharmacology Natural product biology Molecular Structure Organic Chemistry General Medicine biology.organism_classification Antimicrobial Phenanthridines Biochemistry chemistry Hepatocytes Comet Assay Growth inhibition Palladium |
| Zdroj: | European journal of medicinal chemistry. 48 |
| ISSN: | 1768-3254 |
| Popis: | In 1991, WHO recognized the resurgence of tuberculosis as a global health problem. Although modern chemotherapy is effective against the causative pathogen Mycobacterium tuberculosis, the current drug regimens have failed to eradicate the disease. The success of the pathogen, partially attributed to drug resistance, necessitates the development of novel anti-tuberculosis drugs. Benzo[j]phenanthridine-7,12-diones, tetracyclic derivatives of the natural product benz[g]isoquinoline-5,10-dione, were conveniently synthesized via palladium-catalyzed intramolecular cyclization of N-methanesulfonyl-3-bromo-2-(arylamino)methyl-1,4-naphthoquinones. Here we report on the bioactivity of eight benzo[j]phenanthridine-7,12-dione derivatives as candidate drug molecules against M. tuberculosis and on their cytotoxicity on C3A human hepatocytes. The strongest antimicrobial activity (as detected by growth inhibition of bacteria, using luminometry and BACTEC 460-TB) and lowest cytotoxicity was found for 3-methylbenzo[j]phenanthridine-7,12-dione 5e, which was also effective in targeting intracellular M. tuberculosis (in murine J774 macrophages) and was not genotoxic for C3A hepatocytes. |
| Databáze: | OpenAIRE |
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