Glucose-lowering properties of vanadium compounds: comparison of coordination complexes with maltol or kojic acid as ligands.
Bis(kojato)oxovanadium(IV) [abbreviated VO(ka)2], a close chemical analog of the insulin-mimetic lead compound bis(maltolato)oxovanadium(IV)--abbreviated BMOV or VO(ma)2--is reported and its reaction chemistry and insulin-mimetic properties are presented. VO(ka)2 [log K1 = 7.61(10), log K2 = 6.89(6), log beta 2 = 14.50(16)] has a reaction chemistry which directly parallels that of VO(ma)2. In aqueous solution it is more slowly oxidized by molecular oxygen to [VO2(ka)2]- than is VO(ma)2 to [VO2(ma)2]-. Variable pH electrochemistry and variable pH 51V NMR of solutions of VO(ka)2 are presented and contrasted with the corresponding results for VO(ma)2. Time course studies (24 hr) in STZ-diabetic rats following the oral or i.p. administration of VO(ka)2, VO(ma)2, VO2+ (vanadyl) as vanadyl sulfate (VOSO4), and [VO2(ma)2]- as its [NH4]+ salt have been performed, as have chronic oral studies comparing VO(ka)2 and VO(ma)2 over a six week period. In all studies, the most potent form of vanadium was the neutrally charged, water soluble, complex VO(ma)2.
Yuen
V G
VG
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Caravan
P
P
Gelmini
L
L
Glover
N
N
McNeill
J H
JH
Setyawati
I A
IA
Zhou
Y
Y
Orvig
C
C
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D011753:Pyrones / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions; D013329:Structure-Activity Relationship; D013997:Time Factors
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009942:Organometallic Compounds; D011753:Pyrones; D012996:Solutions; C108977:bis(kojato)oxovanadium(IV); C008316:maltol; C011890:kojic acid