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1,2,3,4,8,9,10,11-Octahydrobenzo[j]phenanthridine-7,12-diones as new leads against Mycobacterium tuberculosis

(2014) JOURNAL OF MEDICINAL CHEMISTRY. 57(7). p.2895-2907
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Organization
Abstract
Tuberculosis (TB) continues to be a worldwide health problem with over 1.4 million deaths each year. Despite efforts to develop more effective vaccines, more reliable diagnostics, and chemotherapeutics, tuberculosis remains a threat to global health, fueled by the HIV pandemic and the rapid generation of drug resistance. The exploration of novel drugs to serve as a companion drug for existing drugs is of paramount importance. As part of our program to design new 2-aza-anthraquinones with antimycobacterial activity, various tetrahydro- and octahydrobenzo[j]phenanthridinediones were synthesized. These compounds showed high in vitro potency against Mycobacterium tuberculosis, the etiological agent of TB and against other clinically relevant mycobacterial species at submicromolar concentrations. The susceptibility of a multidrug resistant strain toward these compounds and their ability to target intracellular replicating Mycobacterium tuberculosis was demonstrated. Next to the acute toxicity, the genotoxicity of these compounds was investigated. Often overlooked in studies, genotoxicity could be dismissed for the investigated compounds, making them a promising scaffold in TB drug research.
Keywords
ASSAY, AGENTS, SYSTEM, DERIVATIVES, PATHOGENESIS, MACROPHAGES, ANGUCYCLINONE, ANALOGS, BIOLOGICAL EVALUATION, INFECTION

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Citation

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MLA
Cappoen, Davie, Pieter Claes, Jan Jacobs, et al. “1,2,3,4,8,9,10,11-Octahydrobenzo[j]phenanthridine-7,12-diones as New Leads Against Mycobacterium Tuberculosis.” JOURNAL OF MEDICINAL CHEMISTRY 57.7 (2014): 2895–2907. Print.
APA
Cappoen, D., Claes, P., Jacobs, J., Anthonissen, R., Mathys, V., Verschaeve, L., Huygen, K., et al. (2014). 1,2,3,4,8,9,10,11-Octahydrobenzo[j]phenanthridine-7,12-diones as new leads against Mycobacterium tuberculosis. JOURNAL OF MEDICINAL CHEMISTRY, 57(7), 2895–2907.
Chicago author-date
Cappoen, Davie, Pieter Claes, Jan Jacobs, Roel Anthonissen, Vanessa Mathys, Luc Verschaeve, Kris Huygen, and Norbert De Kimpe. 2014. “1,2,3,4,8,9,10,11-Octahydrobenzo[j]phenanthridine-7,12-diones as New Leads Against Mycobacterium Tuberculosis.” Journal of Medicinal Chemistry 57 (7): 2895–2907.
Chicago author-date (all authors)
Cappoen, Davie, Pieter Claes, Jan Jacobs, Roel Anthonissen, Vanessa Mathys, Luc Verschaeve, Kris Huygen, and Norbert De Kimpe. 2014. “1,2,3,4,8,9,10,11-Octahydrobenzo[j]phenanthridine-7,12-diones as New Leads Against Mycobacterium Tuberculosis.” Journal of Medicinal Chemistry 57 (7): 2895–2907.
Vancouver
1.
Cappoen D, Claes P, Jacobs J, Anthonissen R, Mathys V, Verschaeve L, et al. 1,2,3,4,8,9,10,11-Octahydrobenzo[j]phenanthridine-7,12-diones as new leads against Mycobacterium tuberculosis. JOURNAL OF MEDICINAL CHEMISTRY. 2014;57(7):2895–907.
IEEE
[1]
D. Cappoen et al., “1,2,3,4,8,9,10,11-Octahydrobenzo[j]phenanthridine-7,12-diones as new leads against Mycobacterium tuberculosis,” JOURNAL OF MEDICINAL CHEMISTRY, vol. 57, no. 7, pp. 2895–2907, 2014.
@article{5708888,
  abstract     = {Tuberculosis (TB) continues to be a worldwide health problem with over 1.4 million deaths each year. Despite efforts to develop more effective vaccines, more reliable diagnostics, and chemotherapeutics, tuberculosis remains a threat to global health, fueled by the HIV pandemic and the rapid generation of drug resistance. The exploration of novel drugs to serve as a companion drug for existing drugs is of paramount importance. As part of our program to design new 2-aza-anthraquinones with antimycobacterial activity, various tetrahydro- and octahydrobenzo[j]phenanthridinediones were synthesized. These compounds showed high in vitro potency against Mycobacterium tuberculosis, the etiological agent of TB and against other clinically relevant mycobacterial species at submicromolar concentrations. The susceptibility of a multidrug resistant strain toward these compounds and their ability to target intracellular replicating Mycobacterium tuberculosis was demonstrated. Next to the acute toxicity, the genotoxicity of these compounds was investigated. Often overlooked in studies, genotoxicity could be dismissed for the investigated compounds, making them a promising scaffold in TB drug research.},
  author       = {Cappoen, Davie and Claes, Pieter and Jacobs, Jan and Anthonissen, Roel and Mathys, Vanessa and Verschaeve, Luc and Huygen, Kris and De Kimpe, Norbert},
  issn         = {0022-2623},
  journal      = {JOURNAL OF MEDICINAL CHEMISTRY},
  keywords     = {ASSAY,AGENTS,SYSTEM,DERIVATIVES,PATHOGENESIS,MACROPHAGES,ANGUCYCLINONE,ANALOGS,BIOLOGICAL EVALUATION,INFECTION},
  language     = {eng},
  number       = {7},
  pages        = {2895--2907},
  title        = {1,2,3,4,8,9,10,11-Octahydrobenzo[j]phenanthridine-7,12-diones as new leads against Mycobacterium tuberculosis},
  url          = {http://dx.doi.org/10.1021/m401735w},
  volume       = {57},
  year         = {2014},
}

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