title: Selective activity against Mycobacteriumtuberculosis of new quinoxaline 1,4-di-N-oxides.
abstract: New series of 3-phenylquinoxaline 1,4-di-N-oxide with selective activity against Mycobacterium tuberculosis have been prepared and evaluated. Thirty-four of the seventy tested compounds showed an MIC value less than 0.2 microg/mL, a value on the order of the MIC of rifampicin. Furthermore, 45% of the evaluated derivatives showed a good in vitro activity/toxicity ratio. The most active and selective compounds carry a fluorine atom in the quinoxaline 7-position or in the phenyl substituent para-position. In conclusion, the potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for synthesizing new analogues, particularly compound 7-methyl-3-(4'-fluoro)phenylquinoxaline-2-carbonitrile 1,4-di-N-oxide (MIC <0.2 microg/mL and SI > 500).
authors.affiliation: Unidad de Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada (CIFA), University of Navarra, C/Irunlarrea s/n, 31080 Pamplona, Spain. cifa@unav.es
authors.forename: Esther
authors.initials: E
authors.lastname: Vicente
authors.forename: Silvia
authors.initials: S
authors.lastname: Pérez-Silanes
authors.forename: Lidia M
authors.initials: LM
authors.lastname: Lima
authors.forename: Saioa
authors.initials: S
authors.lastname: Ancizu
authors.forename: Asunción
authors.initials: A
authors.lastname: Burguete
authors.forename: Beatriz
authors.initials: B
authors.lastname: Solano
authors.forename: Raquel
authors.initials: R
authors.lastname: Villar
authors.forename: Ignacio
authors.initials: I
authors.lastname: Aldana
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D005461:Fluorine; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D011810:Quinoxalines; D005461:Fluorine