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 VIV complexes. In particular, the insulin-mimetic activity of [VIV(taci)2]4+, [VIV(inoH−3)2]2−, [VIV(dhab)2], [VIV(hyphPh)2], [VIV(cat)3]2− and [VIV(pdbh)2] – where taci is 1,3,5-triamino-1,3,5-trideoxy-cis-inositol, ino is cis-inositol, H2dhab is 2,2′-dihydroxyazobenzene, H2hyphPh 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 [VIV(pdbh)2], [VIV(cat)3]2− and [VIV(hyphPh)2], which at the physiological pH convert to the corresponding VIVO 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 VIVO 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.