1,4-Bis(alkylamino)benzo[g]phthalazines able to form dinuclear complexes of Cu(II) which as free ligands behave as SOD inhibitors and show efficient in vitro activity against Trypanosoma cruzi.
The synthesis of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1-3 is reported, and their ability to form dinuclear complexes with Cu(II) assayed. The geometry of the complexes is dependent on the nature of the electron-donor sites at the sidechains. Compounds 1 and 2, that contain sp3 or sp2 nitrogens at the end of the alkylamino groups, originate monopodal dinuclear complexes which seem to include endogenous OH bridges, and the sidechains seem to actively participate in complexation. However, the substitution of nitrogen by oxygen in 3 leads to a tripodal dinuclear complex in which the sidechains are not involved. The in vitro antiparasitic activity on Trypanosoma cruzi epimastigotes and amastigotes and the SOD activity inhibition have been evaluated for compounds 1-3, and, as expected, 1 and 2 show in all cases relevant results, whereas 3 is always the less active among the three substrates tested.
Rodríguez-Ciria
Marinela
M
Departamento de Química Orgánica I, Facultad de Química, Universidad Complutense, 28040 Madrid, Spain.
Sanz
Ana M
AM
Yunta
María J R
MJ
Gómez-Contreras
Fernando
F
Navarro
Pilar
P
Sánchez-Moreno
Manuel
M
Boutaleb-Charki
Samira
S
Osuna
Antonio
A
Castiñeiras
Alfonso
A
Pardo
Mercedes
M
Cano
Carmen
C
Campayo
Lucrecia
L
D000818:Animals; D002522:Chlorocebus aethiops; D003300:Copper / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D010793:Phthalazines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors*; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014709:Vero Cells
D004791:Enzyme Inhibitors; D008024:Ligands; D010793:Phthalazines; D003300:Copper; C043388:phthalazine; D013482:Superoxide Dismutase