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Title
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Synthesis and anti-tubercular activity of -arylbenzo[g]isoquinoline-5,10-dione-3-iminium bromides
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Author
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Abstract
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| Tuberculosis has remained a challenge for medicinal chemists worldwide. In the framework of a collaborative program to identify and evaluate novel antitubercular candidate compounds, the biological properties of benzo[g]isoquinoline-5,10-diones have been found to be very promising. In this paper we have further expanded the library by incorporation of an amidinium moiety into the benzo[g] isoquinoline-5,10-dione scaffold. The presence of this functional group also increased the solubility of the quinones in polar solvents. To this purpose N-2-arylbenzo[g]isoquinoline-5,10-dione-3-iminium bromides were synthesized in a straightforward way by means of a reaction of anilines with 2-(bromomethyl)-3-(cyanomethyl)-1,4-dimethoxynaphthalene. Following the biological evaluation, N-2-(4-chlorophenyl)-5,10-dioxobenzo[g]isoquinoline-3(2H)-iminium bromide (MIC = 1.16 mu M, CC50 = 28.51 mu M, SI = 24.58) was selected as the most promising representative. Apart from the nano-molar anti-mycobacterial activity, the compound was able to target intracellular residing Mycobacterium tuberculosis and the susceptibility of a multi-drug-resistant strain towards the compound was confirmed. |
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Language
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English
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Source (journal)
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Organic and biomolecular chemistry. - Cambridge, 2003, currens
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Publication
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Cambridge
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Royal Society of Chemistry
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2016
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ISSN
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1477-0520
[print]
1477-0539
[online]
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DOI
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10.1039/C5OB02138C
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Volume/pages
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14
:6
(2016)
, p. 2041-2051
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ISI
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000369601600018
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Pubmed ID
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26763748
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Full text (Publisher's DOI)
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Full text (open access)
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