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

• Published in: Dalton transactions : an international journal of inorganic chemistry Vol. 43; no. 19; pp. 6965 - 6972
• Main Authors: Yoshikawa, Yutaka, Sakurai, Hiromu, Crans, Debbie C, Micera, Giovanni, Garribba, Eugenio
• Format: Journal Article
• Language: English
• Published: England 21.05.2014
• Subjects: Adipocytes - cytology; Adipocytes - drug effects; Animals; Biocompatible Materials - chemical synthesis; Biocompatible Materials - chemistry; Biocompatible Materials - pharmacology; Cell Line; Cell Survival - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Fatty Acids, Nonesterified - chemistry; Fatty Acids, Nonesterified - metabolism; Hydrogen-Ion Concentration; Hypoglycemic Agents - chemical synthesis; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Oxidation-Reduction; Rats; Vanadium - chemistry
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c3dt52895b

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- ci s-inositol, ino is ci s-inositol, H 2 dhab is 2,2′-dihydroxyazobenzene, H 2 hyph Ph is 3,5-bis(2-hydroxyphenyl)-1 H -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 (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 VOSO 4 . 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. The transformation of non-oxido V IV to oxido V IV species under physiological conditions is necessary for a vanadium compound to exhibit pharmacological anti-diabetic activity.