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(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.

Structural and spectroscopic studies of a rare non-oxido V(v) complex crystallized from aqueous solution

“…Lastly, in a detailed study carried out by Yoshikawa and co-workers of six different crystalline non-oxido V( iv ) complexes, very compelling evidence was provided suggesting that only those complexes that transformed to their vanadyl (oxido) form at physiological pH exhibited insulin mimetic behavior 37. However, such a study could not be carried out with V( v ) complexes partly because very few non-oxido V( v ) complexes have been identified.…”

Behavior of the potential antitumor VIVO complexes formed by flavonoid ligands. 2. Characterization of sulfonate derivatives of quercetin and morin, interaction with the bioligands of the plasma and preliminary biotransformation studies

“…The assumption that the V IV O complexes reach the target cells in the same form as they are administrated is an oversimplification [36]. The biotransformation in the organism is also important in the evaluation of the transport and drug metabolism.…”

Vanadium and proteins: Uptake, transport, structure, activity and function

“…Inter-conversion between V IV and V V may thus be fast and easy in physiological conditions. It was first suggested by Crans et al [5] that, besides monovanadate(V), V IV O(OH) 3 − may also mimic phosphate [5] [10] [11]. Therefore, the fact that V IV O-species also inhibit different enzymes (in some cases with a greater potency than vanadate(V)) may be based on the formation of V IV O(OH) 3 − and its resemblance to vanadate(V), namely for cysteine-based phosphatases.…”