Vanadium compounds as therapeutic agents: some chemical and biochemical studies.
The behaviour of three vanadium(V) systems, namely the pyridinone (V(V)-dmpp), the salicylaldehyde (V(V)-salDPA) and the pyrimidinone (V(V)-MHCPE) complexes, is studied in aqueous solutions, under aerobic and physiological conditions using (51)V NMR, EPR and UV-Visible (UV-Vis) spectroscopies. The speciations for the V(V)-dmpp and V(V)-salDPA have been previously reported. In this work, the system V(V)-MHCPE is studied by pH-potentiometry and (51)V NMR. The results indicate that, at pH ca. 7, the main species present are (V(V)O(2))L(2) and (V(V)O(2))LH(-1) (L=MHCPE(-)) and hydrolysis products, similar to those observed in aqueous solutions of V(V)-dmpp. The latter species is protonated as the pH decreases, originating (V(V)O(2))L and (V(V)O(2))LH. All the V(V)-species studied are stable in aqueous media with different compositions and at physiological pH, including the cell culture medium. The compounds were screened for their potential cytotoxic activity in two different cell lines. The toxic effects were found to be incubation time and concentration dependent and specific for each compound and type of cells. The HeLa tumor cells seem to be more sensitive to drug effects than the 3T3-L1 fibroblasts. According to the IC(50) values and the results on reversibility to drug effects, the V(V)-species resulting from the V(V)-MHCPE system show higher toxicity in the tumor cells than in non-tumor cells, which may indicate potential antitumor activity.
Faneca
H
H
Departamento de Bioquímica e Centro de Neurociências e Biologia Celular, Faculdade de Ciências e Tecnologia, Universidade de Coimbra, Apartado 3126, Coimbra, Portugal.
Figueiredo
V A
VA
Tomaz
Isabel
I
Gonçalves
Gisela
G
Avecilla
Fernando
F
Pedroso de Lima
M C
MC
Geraldes
Carlos F G C
CF
Pessoa
João Costa
JC
Castro
M Margarida C A
MM
D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D013329:Structure-Activity Relationship; D014639:Vanadium / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014639:Vanadium