Quinoxaline N,N'-dioxide derivatives and related compounds as growth inhibitors of Trypanosoma cruzi. Structure-activity relationships.
Quinoxaline derivatives presented good inhibitor activity of growth of Trypanosoma cruzi in in vitro assays. The 50% inhibitory doses were of the same order of that of Nifurtimox. Derivative 13, a quinoxaline N,N'-dioxide derivative, and the reduced derivatives 19 and 20 were the most cytotoxic compounds against the protozoan. Structural requirements for optimal activity were studied by computational methods. From statistical analysis we could establish a multiple correlation between activity and lipophilic properties and LUMO energy.
Aguirre
Gabriela
G
Departamento de Química Orgánica, Facultad de Química, Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.
Cerecetto
Hugo
H
Di Maio
Rossanna
R
González
Mercedes
M
Alfaro
María Elena Montoya
ME
Jaso
Andrés
A
Zarranz
Belén
B
Ortega
Miguel Angel
MA
Aldana
Ignacio
I
Monge-Vega
Antonio
A
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003497:Cyclic N-Oxides / Q000138:chemical synthesis / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D009547:Nifurtimox / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
D003497:Cyclic N-Oxides; D011810:Quinoxalines; D014344:Trypanocidal Agents; D009547:Nifurtimox