Pyrimido[1,2-a]quinoxaline 6-oxide and phenazine 5,10-dioxide derivatives and related compounds as growth inhibitors of Trypanosoma cruzi.
Two different families of N-oxide containing heterocycles were evaluated as in vitro growth inhibitors of T. cruzi. Both families of heterocycles were selected from our in-house library of compounds as analogues of active anti-T. cruzi N-oxide containing heterocycles. Derivatives from pyrimido[1,2-a]quinoxaline 6-oxide family were poorly active at the assayed doses. However, phenazine 5,10-dioxide derivatives displayed good to excellent anti-T. cruzi activities. The anti-T. cruzi activity of phenazine derivatives was related to substituent' electronic descriptors, sigma(p)(-). Derivatives 19, 20 and 23 were the most cytotoxic compounds against the protozoan and became excellent hit for further structural modifications.
Lavaggi
María Laura
ML
Departamento de Química Orgánica, Facultad de Química-Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.
Aguirre
Gabriela
G
Boiani
Lucía
L
Orelli
Liliana
L
García
Beatriz
B
Cerecetto
Hugo
H
González
Mercedes
M
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004583:Electrons; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010619:Phenazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000166:cytology / Q000187:drug effects*
D000962:Antimalarials; D003497:Cyclic N-Oxides; D010619:Phenazines; D011810:Quinoxalines