Title
Straightforward palladium-mediated synthesis and biological evaluation of benzo[**j**]phenanthridine-7,12-diones as anti-tuberculosis agentsStraightforward palladium-mediated synthesis and biological evaluation of benzo[**j**]phenanthridine-7,12-diones as anti-tuberculosis agents
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
Department of Biomedical Sciences - other
Publication type
article
Publication
Paris,
Subject
Chemistry
Pharmacology. Therapy
Source (journal)
European journal of medicinal chemistry. - Paris, 1974, currens
Volume/pages
48(2012), p. 57-68
ISSN
0223-5234
ISI
000300484900006
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
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.
E-info
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