Design of vanadium mixed-ligand complexes as potential anti-protozoa agents.
In the search for new therapeutic tools against Chagas' disease (American Trypanosomiasis) four novel mixed-ligand vanadyl complexes, [V(IV)O(L(2)-2H)(L(1))], including a bidentate polypyridyl DNA intercalator (L(1)) and a tridentate salycylaldehyde semicarbazone derivative (L(2)) as ligands were synthesized, characterized by a combination of techniques, and in vitro evaluated. EPR suggest a distorted octahedral geometry with the tridentate semicarbazone occupying three equatorial positions and the polypyridyl ligand coordinated in an equatorial/axial mode. Both complexes including dipyrido[3,2-a: 2',3'-c]phenazine (dppz) as polypyridyl coligand showed IC(50) values in the muM range against Dm28c strain (epimastigotes) of Trypanosoma cruzi, causative agent of the disease, being as active as the anti-trypanosomal reference drug Nifurtimox. To get an insight into the trypanocidal mechanism of action of these compounds, DNA was evaluated as a potential parasite target and EPR, and (51)V NMR experiments were also carried out upon aging aerated solutions of the complexes. Data obtained by electrophoretic analysis suggest that the mechanism of action of these complexes could include DNA interactions.
Benítez
Julio
J
Cátedra de Química Inorgánica, Facultad de Química, Universidad de la República, Gral. Flores 2124, C. C. 1157, Montevideo, Uruguay.
Guggeri
Lucía
L
Tomaz
Isabel
I
Arrambide
Gabriel
G
Navarro
Maribel
M
Pessoa
João Costa
JC
Garat
Beatriz
B
Gambino
Dinorah
D
D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D008024:Ligands; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects; D014639:Vanadium / Q000737:chemistry* / Q000494:pharmacology
D008024:Ligands; D014344:Trypanocidal Agents; D014639:Vanadium