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.The authors thank the Spanish CICYT for the financial support

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.The authors thank the Spanish Comision Interministerial de Ciencia y Tecnologia for the economical support given to this work (SAF99-0066)

Efecto biológico de nuevos compuestos de síntesis y naturales frente a tripanosomátidos

Tesis Univ. Granada. Instituto de Biotecnología. Departamento de Parasitología. Leída el 16 de abril de 201