1,2,5-Oxadiazole N-oxide derivatives and related compounds as potential antitrypanosomal drugs: structure-activity relationships.
The syntheses of a new series of derivatives of 1,2,5-oxadiazole N-oxide, benzo[1,2-c]1,2,5-oxadiazole N-oxide, and quinoxaline di-N-oxide are described. In vitro antitrypanosomal activity of these compounds was tested against epimastigote forms of Trypanosoma cruzi. For the most effective drugs, derivatives IIIe and IIIf, the 50% inhibitory dose (ID50) was determined as well as their cytotoxicity against mammalian fibroblasts. Electrochemical studies and ESR spectroscopy show that the highest activities observed are associated with the facile monoelectronation of the N-oxide moiety. Lipophilic-hydrophilic balance of the compounds could also play an important role in their effectiveness as antichagasic drugs.
Cerecetto
H
H
Department of Organic Chemistry, Faculty of Chemistry, University of the Republic, CC 1157, 11800 Montevideo, Uruguay.
Di Maio
R
R
González
M
M
Risso
M
M
Saenz
P
P
Seoane
G
G
Denicola
A
A
Peluffo
G
G
Quijano
C
C
Olea-Azar
C
C
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000737:chemistry; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D005347:Fibroblasts; D020128:Inhibitory Concentration 50; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D014349:Trypanosoma cruzi / Q000187:drug effects
C119476:5(6)-(butylcarbamoyl)benzo(1,2-c)1,2,5-oxadiazole N(1)-oxide; C119477:5(6)-(hexylcarbamoyl)benzo(1,2-c)1,2,5-oxadiazole N(1)-oxide; D003497:Cyclic N-Oxides; D010069:Oxadiazoles; D014344:Trypanocidal Agents