Selective activity against Mycobacteriumtuberculosis of new quinoxaline 1,4-di-N-oxides.
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).
Vicente
Esther
E
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
Pérez-Silanes
Silvia
S
Lima
Lidia M
LM
Ancizu
Saioa
S
Burguete
Asunción
A
Solano
Beatriz
B
Villar
Raquel
R
Aldana
Ignacio
I
Monge
Antonio
A
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
D000995:Antitubercular Agents; D011810:Quinoxalines; D005461:Fluorine