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Title
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Synthesis and antitubercular activity of 1-and 3-substituted benzo[g]isoquinoline-5,10-diones
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Author
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Abstract
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| In this study, a small library of twenty benzo[g] isoquinoline-5,10-diones were synthesized in a novel straightforward approach, starting from 2-methyl-1,4-naphthoquinone (vitamin K). An intramolecular Heck reaction of a N-vinylacetamide was a crucial step in the synthetic route, at which the combination of cesium carbonate and a bulky, electron rich trialkylphosphine ((BuCy2P)-Bu-t center dot HBF4) provided high 6-endotrig selectivity. The anti-tubercular activity against Mycobacterium tuberculosis H37Ra and acute cytotoxicity against J774 A. 1 macrophages were studied. From the structure activity relationship, it could be derived that in general the substitution of position 3 yielded analogs with a higher antitubercular potency. Among these, two analogs, 27a and 27b, showed remarkable activity with minimal inhibition concentrations of respectively 28.92 mu M and 1.05 mu M, and acute cytotoxic concentrations of > 128 mu M and 34.85 mu M. In addition, the analogs and their possible metabolites were evaluated using a Vitotox (TM) assay to study the possibility of genotoxicity. Results indicated that none of the evaluated analogs and their possible metabolites showed early signs of genotoxicity. |
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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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2019
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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/C8OB02690D
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Volume/pages
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17
:11
(2019)
, p. 2923-2939
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ISI
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000461223700011
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Pubmed ID
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30801604
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Full text (Publisher's DOI)
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Full text (open access)
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