Anti-T. cruzi activities and QSAR studies of 3-arylquinoxaline-2-carbonitrile di-N-oxides.
In a continuing effort to identify new active compounds for combating Chagas disease and other neglected diseases, our research group synthesized and evaluated 23 3-arylquinoxaline-2-carbonitrile di-N-oxides against Trypanosoma cruzi. Five of them presented IC(50) values of the same magnitude as the standard drug Nifurtimox, making them valid as new lead compounds. The optimized molecular structures of 23 derivatives represented by 1497 types of DRAGON descriptors were subjected to linear regression analysis, and the derived QSAR was shown to be predictive. In this way, we achieved a rational guide for the proposal of new candidate structures whose activities still remain unknown.
Vicente
Esther
E
Unidad de Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada, University of Navarra, C/Irunlarrea s/n, 31008 Pamplona, Spain. estherviccem@gmail.com
Duchowicz
Pablo R
PR
Benítez
Diego
D
Castro
Eduardo A
EA
Cerecetto
Hugo
H
González
Mercedes
M
Monge
Antonio
A
D009547:Nifurtimox / Q000737:chemistry / Q000494:pharmacology; D010087:Oxides / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D011810:Quinoxalines / Q000737:chemistry* / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects*
D010087:Oxides; D011810:Quinoxalines; D014344:Trypanocidal Agents; C003282:quindoxin; D009547:Nifurtimox