title: Design and synthesis of novel quinoxaline derivatives as potential candidates for treatment of multidrug-resistant and latent tuberculosis.
abstract: 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 Mycobacterium tuberculosis and compound 21 was bactericidal. Therefore, quinoxaline derivatives could be considered for making further advances in the future development of antimycobacterial agents.
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain; Institute of Tropical Health, University of Navarra, Irunlarrea s/n, E-31008 Pamplona, Spain.
authors.forename: Mery
authors.initials: M
authors.lastname: Santivañez-Veliz
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain; Institute of Tropical Health, University of Navarra, Irunlarrea s/n, E-31008 Pamplona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pérez-Silanes
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Torres
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain; Institute of Tropical Health, University of Navarra, Irunlarrea s/n, E-31008 Pamplona, Spain. Electronic address: emviguri@unav.es.
authors.forename: Elsa
authors.initials: E
authors.lastname: Moreno-Viguri
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D003497:Cyclic N-Oxides / Q000737:chemistry / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D055985:Latent Tuberculosis / Q000188:drug therapy; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D003497:Cyclic N-Oxides; D011810:Quinoxalines; C003282:quindoxin
keywords: Antimycobacterial; Intracellular activity; Quinoxaline; Tuberculosis