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

Abstract

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^IVO 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^IVO 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.