title: Comparison of anti-hyperglycemic effect amongst vanadium, molybdenum and other metal maltol complexes.
abstract: A wide variety of vanadium-containing complexes have been tested, both in vivo and in vitro, as possible therapeutic agents for the oral treatment of type 2 diabetes mellitus. None so far has surpassed bis(maltolato)oxovanadium(IV) (BMOV) for glucose- and lipid-lowering in an orally available formulation. Ligand choice is clearly an important factor in pharmacological efficacy of vanadium compounds as insulin enhancing agents. In this study, we kept the ligand and dose the same, varying instead the metal ion bound to the maltolato ligand in a series of binary complexes of neutral charge. A requirement for vanadyl ion as the metal ion of choice was apparent; no other metal ion tested served as a suitable substitute. Amongst [MoO(2)](2+), Co(II), Cu(II), Cr(III), and Zn(II), only [MoO(2)](2+) and Co(II) showed any hypoglycemic activity at the ED(50) dose for bis(maltolato)oxovanadium(IV), 0.6 mmolkg(-1) by oral gavage in streptozotocin (STZ)-diabetic rats within 72 h of administration of compound.
authors.affiliation: Medicinal Inorganic Chemistry Group, Chemistry Department, University of British Columbia, Vancouver, BC, Canada V6T 1Z1. kthompso@chem.ubc.ca
authors.forename: Katherine H
authors.initials: KH
authors.lastname: Thompson
authors.forename: Jessica
authors.initials: J
authors.lastname: Chiles
authors.forename: Violet G
authors.initials: VG
authors.lastname: Yuen
authors.forename: Jeremy
authors.initials: J
authors.lastname: Tse
authors.forename: John H
authors.initials: JH
authors.lastname: McNeill
authors.forename: Chris
authors.initials: C
authors.lastname: Orvig
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D008982:Molybdenum; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014638:Vanadates / Q000494:pharmacology; D014639:Vanadium
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009942:Organometallic Compounds; D011753:Pyrones; D014639:Vanadium; C074212:bis(maltolato)oxovanadium(IV); C008316:maltol; D014638:Vanadates; D008982:Molybdenum