Behavior of the potential antitumor V(IV)O complexes formed by flavonoid ligands. 3. Antioxidant properties and radical production capability.

The radical production capability and the antioxidant properties of some V(IV)O complexes formed by flavonoid ligands were examined. In particular, the bis-chelated species of quercetin (que), [VO(que)2](2-), and morin (mor), [VO(mor)2], were evaluated for their capability to reduce the stable radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and produce the hydroxyl radical (•)OH by Fenton-like reactions, where the reducing agent is V(IV)O(2+). The results were compared with those displayed by other V(IV)O complexes, such as [VO(H2O)5](2+), [VO(acac)2] (acac=acetylacetonate) and [VO(cat)2](2-) (cat=catecholate). The capability of the V(IV)O flavonoids complexes to reduce DPPH is much larger than that of the V(IV)O species formed by non-antioxidant ligands and it is due mainly to the flavonoid molecule. Through the 5,5-dimethyl-1-pyrroline N-oxide (DMPO) spin trapping assay of the hydroxyl radical it was possible to demonstrate that in acidic solution V(IV)O(2+) has an effectiveness in producing (•)OH radicals comparable to that of Fe(2+). When V(IV)O complexes of flavonoids were taken into account, the amount of hydroxyl radicals produced in Fenton-like reactions depends on the specific structure of the ligand and on their capability to reduce H2O2 to give (•)OH. Both the formation of reactive oxygen species (ROS) under physiological conditions by V(IV)O complexes of flavonoid ligands and their radical scavenging capability can be put in relationship with their antitumor effectiveness and it could be possible to modulate these actions by changing the features of the flavonoid coordinated to the V(IV)O(2+) ion, such as the entity, nature and position of the substituents and the number of phenolic groups.