Journal
COORDINATION CHEMISTRY REVIEWS
Volume 245, Issue 1-2, Pages 31-37Publisher
ELSEVIER SCIENCE SA
DOI: 10.1016/S0010-8545(03)00031-6
Keywords
vanadyl-pyridone complexes; insulin-mimetic activity; antidiabetic activity; chemical specification; adipocytes; blood circulation monitoring-electron paramagnetic resonance (BCM-EPR)
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To treat both insulin-dependent type 1 and non-insulin-dependent type 2 diabetic mellitus, two potent antidiabetic vanadyl pyridone complexes, bis(1-oxy-2-pyridinethiolato)oxovanadium(IV), (VO(opt)(2)) and bis(1-oxy-2-pyridonato)oxovanadium(IV), (VO(opd)(2)), were proposed on the basis of the results of diabetic model animals by using a concept of equivalent transformation, which has been proved to be effective in changing the chemical property of a compound. Their physico-chemical properties, chemical specications, in vitro insulin-mimetic activity in isolated rat adipocytes, in vivo antidiabetic activity in both type 1 and type 2 diabetic animals, and metallokinetic feature of the vanadyl species in the blood flow of live rats by using blood circulation monitoring-electron paramagnetic resonance (BCM-EPR) were examined. Both complexes exhibited higher in vitro insulin-mimetic activity than VOSO4, and the activity of VO(opt)(2) was superior to that of VO(opd)(2). However, on oral administration to type 1 diabetic rats, VO(opd)(2) was more effective at lower dose than VO(opt)(2). The results are supported by chemical specifications and metallokinetic (kinetic of metal disposition) parameters. (C) 2003 Elsevier B.V. All rights reserved.
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