Structural and redox requirements for the action of anti-diabetic vanadium compounds

This study presents the first systematic investigation of the anti-diabetic properties of non-oxido V(IV) complexes. In particular, the insulin-mimetic activity of [V(IV)(taci)2](4+), [V(IV)(inoH-3)2](2-), [V(IV)(dhab)2], [V(IV)(hyph(Ph))2], [V(IV)(cat)3](2-) and [V(IV)(pdbh)2]--where taci is 1,3,5-triamino-1,3,5-trideoxy-cis-inositol, ino is cis-inositol, H2dhab is 2,2'-dihydroxyazobenzene, H2hyph(Ph) is 3,5-bis(2-hydroxyphenyl)-1H-1,2,4-triazole, H2cat is catechol and H2pdbh is pentan-2,4-dione benzoylhydrazone--was evaluated in terms of free fatty acid (FFA) release. Among the six compounds examined, only [V(IV)(pdbh)2], [V(IV)(cat)3](2-) and [V(IV)(hyph(Ph))2], which at the physiological pH convert to the corresponding V(IV)O complexes, were found to exhibit a significant insulin-mimetic activity compared to VOSO4. In contrast, [V(taci)2](4+), [V(inoH-3)2](2-) and [V(dhab)2], which at pH 7.4 keep their 'bare' non-oxido structure, did not cause any inhibition of FFA. The results, therefore, suggest that a V(IV)O functionality is necessary for vanadium complexes to exhibit anti-diabetic effects. This agrees with the notion that the biotransformations of V compounds in the organism are more important than the nature of the species.