Benzo[1,2-c]1,2,5-oxadiazole N-oxide derivatives as potential antitrypanosomal drugs. Structure-activity relationships. Part II.
The preparation of new derivatives of benzo[1,2-c]1,2,5-oxadiazole N-oxide is described. These derivatives were chosen in order to investigate and confirm previous structural features found necessary to display an adequate antitrypanosomal activity. The compounds synthesized were tested in vitro against epimastigote forms of Trypanosoma cruzi. The presence of a bromine atom in the benzo system produced compounds less active than the corresponding de-halo analogues. However, 5-(bromomethyl)-7-bromobenzo[1,2-c]oxadiazole N-oxide (23) was the most cytotoxic compound against T. cruzi. For this, the 50% inhibitory dose (ID50) was determined, it was of the same order as that of Nifurtimox. From statistical analysis we could establish a relationship between lipophilic-hydrophilic balance of the derivatives with their effectiveness as antichagasic compounds.
Aguirre
Gabriela
G
Departamento de Química Orgánica, Facultad de Química-Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
Cerecetto
Hugo
H
Di Maio
Rossanna
R
González
Mercedes
M
Porcal
Williams
W
Seoane
Gustavo
G
Ortega
Miguel A
MA
Aldana
Ignacio
I
Monge
Antonio
A
Denicola
Ana
A
D000818:Animals; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects
D003497:Cyclic N-Oxides; D010069:Oxadiazoles; D014344:Trypanocidal Agents; C472528:benzo(1,2-c)1,2,5-oxadiazole N-oxide