Efficient inhibition of iron superoxide dismutase and of Trypanosoma cruzi growth by benzo[g]phthalazine derivatives functionalized with one or two imidazole rings.
The synthesis and trypanosomatic behavior of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1- 4 containing the biologically significant imidazole ring are reported. In vitro antiparasitic activity against Trypanosoma cruzi epimastigotes is remarkable, especially for compound 2, whereas toxicity against Vero cells is very low. Conversion of epimastigotes to metacyclic forms in the presence of the tested compounds causes significant decreases in the amastigote and trypomastigote numbers. Fe-SOD inhibition is noteworthy, whereas effect on human Cu/Zn-SOD is negligible.
Sanz
Ana M
AM
Departamento de Química Orgánica I, Facultad de Química, Universidad Complutense, Madrid, Spain.
Gómez-Contreras
Fernando
F
Navarro
Pilar
P
Sánchez-Moreno
Manuel
M
Boutaleb-Charki
Samira
S
Campuzano
Jose
J
Pardo
Mercedes
M
Osuna
Antonio
A
Cano
Carmen
C
Yunta
María J R
MJ
Campayo
Lucrecia
L
D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010793:Phthalazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development; D014709:Vero Cells / Q000187:drug effects
D000977:Antiparasitic Agents; D007093:Imidazoles; D010793:Phthalazines; D013482:Superoxide Dismutase