< Terug naar vorige pagina


Synthesis and antitubercular activity of 1-and 3-substituted benzo[g]isoquinoline-5,10-diones

Tijdschriftbijdrage - Tijdschriftartikel

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.
Tijdschrift: Organic and biomolecular chemistry
ISSN: 1477-0520
Volume: 17
Pagina's: 2923 - 2939
Jaar van publicatie:2019
Trefwoorden:A1 Journal article
BOF-publication weight:1
CSS-citation score:1
Authors from:Higher Education