Santivañez-Veliz M, Pérez-Silanes S, Torres E, Moreno-Viguri E. Design and synthesis of novel quinoxaline derivatives as potential candidates for treatment of multidrug-resistant and latent tuberculosis. Bioorg Med Chem Lett 2016;26(9):2188–2193
Twenty-four quinoxaline derivatives were evaluated for their antimycobacterial
activity using BacTiter-Glo microbial cell viability assay. Five compounds showed
MIC values < 3.1 μM and IC50 values < 1.5 μM in primary screening and therefore,
they were moved on for further evaluation. Compounds 21 and 18 stand out, showing
MIC values of 1.6 μM and IC50 values of 0.5 and 1.0 μM respectively. Both
compounds were the most potent against three evaluated drug-resistant strains.
Moreover, they exhibited intracellular activity in infected macrophages, considering
log-reduction and cellular viability. In addition, compounds 16 and 21 were potent
against non-replicating M. Tb. and compound 21 was bactericidal. Therefore,
quinoxaline derivatives could be considered for making further advances in the future
development of antimycobacterial agents.