1613190-08-1Relevant articles and documents
Azaaurones as Potent Antimycobacterial Agents Active against MDR- and XDR-TB
Campani?o, André,Carrasco, Marta P.,Njoroge, Mathew,Seldon, Ronnett,Chibale, Kelly,Perdig?o, Jo?o,Portugal, Isabel,Warner, Digby F.,Moreira, Rui,Lopes, Francisca
, p. 1537 - 1546 (2019/08/02)
Herein we report the screening of a small library of aurones and their isosteric counterparts, azaaurones and N-acetylazaaurones, against Mycobacterium tuberculosis. Aurones were found to be inactive at 20 μm, whereas azaaurones and N-acetylazaaurones emerged as the most potent compounds, with nine derivatives displaying MIC99 values ranging from 0.4 to 2.0 μm. In addition, several N-acetylazaaurones were found to be active against multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical M. tuberculosis isolates. The antimycobacterial mechanism of action of these compounds remains to be determined; however, a preliminary mechanistic study confirmed that they do not inhibit the mycobacterial cytochrome bc1 complex. Additionally, microsomal metabolic stability and metabolite identification studies revealed that N-acetylazaaurones are deacetylated to their azaaurone counterparts. Overall, these results demonstrate that azaaurones and their N-acetyl counterparts represent a new entry in the toolbox of chemotypes capable of inhibiting M. tuberculosis growth.
