Comparison of anti-hyperglycemic effect amongst vanadium, molybdenum and other metal maltol complexes.
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.
Thompson
Katherine H
KH
Medicinal Inorganic Chemistry Group, Chemistry Department, University of British Columbia, Vancouver, BC, Canada V6T 1Z1. kthompso@chem.ubc.ca
Chiles
Jessica
J
Yuen
Violet G
VG
Tse
Jeremy
J
McNeill
John H
JH
Orvig
Chris
C
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
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009942:Organometallic Compounds; D011753:Pyrones; D014639:Vanadium; C074212:bis(maltolato)oxovanadium(IV); C008316:maltol; D014638:Vanadates; D008982:Molybdenum