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

This study presents the first systematic investigation of the antidiabetic 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(hyphPh)(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, H(2)dhab is 2,2'-dihydroxyazobenzene, H(2)hyph(Ph) is 3,5-bis(2-hydroxyphenyl)-1H-1,2,4-triazole, H(2)cat is catechol and H(2)pdbh 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(hyphPh)(2)], which at the physiological pH convert to the corresponding (VO)-O-IV 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 (VO)-O-IV functionality is necessary for vanadium complexes to exhibit anti-diabetic effects. This agrees with the notion that the biotrans-formations of V compounds in the organism are more important than the nature of the species.