Mechanistic studies on anti-tumor properties of 2-arylcarbonyl-3-trifluoromethylquinoxaline 1,4-di-N-oxide analogs

TOXI 91

Venkatraman Junnotula, vjm94@mizzou.edu1, Kent Gates, GatesK@missouri.edu1, Beatriz Soland2, Adoracion Marin2, Raquel Villar2, Asuncion Burguete2, Esther Vicente2, Sivia Perez-silanes2, Ignacio Aldana2, and Antonio Monge2. (1) Department of Chemistry, University of Missouri-Columbia, 601 S. College Ave, Columbia, MO 65211, (2) Unidad en Investigacion y Desarrollo de medicamentos, University of Navarra, c/Irunlarrea s/n, 31080 Pamplona, Spain, Spain
Quinoxaline N-oxides can display potent antitumor activity. Here, we examined the chemistry underlying the antitumor activity of 2-arylcarbonyl-3-trifluoromethylquino-xaline 1,4-di-N-oxides. We investigated the interaction of quinoxaline analogs with the bioreductive enzyme, NADPH:cytochrome P450 reductase under both aerobic and anaerobic conditions. Under aerobic conditions, quinoxaline N-oxides efficiently generate reactive oxygen species via redox cycling. Under anaerobic conditions, these compounds release hydroxyl radical (or a similarly reactive diffusible oxidant).

 

Poster Session and Awards
6:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- 204 A/B, Poster

Division of Chemical Toxicology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007