@article {2366,
	title = {Calorimetric studies of the interaction between the insulin-enhancing drug candidate bis(maltolato)oxovanadium(IV) (BMOV) and human serum apo-transferrin},
	journal = {Journal of Inorganic Biochemistry},
	volume = {103},
	number = {4},
	year = {2009},
	note = {ISI Document Delivery No.: 429EUTimes Cited: 8Cited Reference Count: 31Bordbar, Abdol-Khalegh Creagh, A. Louise Mohammadi, Fakhrossadat Haynes, Charles A. Orvig, Chris6th International Vanadium SymposiumJUL 17-19, 2008Lisbon, PORTUGALSp. Iss. SI},
	month = {Apr},
	pages = {643-647},
	type = {Proceedings Paper},
	abstract = {Bis(maltolato)oxovanadium(IV) (BMOV), and its ethylmaltol analog, bis(ethymaltolato)oxovanadium(IV) (BEOV), are candidate insulin-enhancing agents for the treatment of type 2 diabetes mellitus; in mid-2008, BEOV advanced to phase 11 clinical testing. The interactions of BMOV and its inorganic congener, vanadyl Sulfate (VOSO4), with human serum apo-transferrin (hTf) were investigated using differential scanning calorimetry (DSC). Addition of BMOV or VOSO4 to apo-hTf resulted in an increase in thermal stability of both the C- and N-lobes of transferrin as a result of binding to either vanadyl compound. A series of DSC thermograms of hTf Solutions containing different molar ratios of BMOV and VOSO4 were used to determine binding constants: at 25 degrees C the binding constants of BMOV to the C- and N-lobes of apo-hTf were found to be 3 (+/- 1) x 10(5) and 1.8 (+/- 0.7) x 10(5) M-1, respectively. The cot-responding values for VOSO4 were 1.7 (+/- 0.3) x 10(5) and 7 (+/- 2) x 10(4) M-1. The results show that the vanadium species initially presented as either BMOV or VOSO4 had similar affinities for human serum transferrin due to oxidation of solvated vanadyl(IV) prior to complexation to transferrin. Binding of metavanadate (VO3-) was confirmed by DSC and isothermal titration calorimetry (ITC) experiments of the interaction between sodium metavanadate (NaVO3) and hTf. (C) 2008 Elsevier Inc. All rights reserved.},
	keywords = {Apo-transferrin, BINDING, BIS(MALTOLATO)OXOVANADIUM(IV), CHEMISTRY, COMPLEXES, Insulin-enhancing, iron, MALTOL, MOLYBDENUM, NICKEL, RATS, STABILITY, VANADIUM},
	isbn = {0162-0134},
	url = {<Go to ISI>://000264904400022},
	author = {Bordbar, A. K. and Creagh, A. L. and Mohammadi, F. and Haynes, C. A. and Orvig, Chris}
}
@article {2637,
	title = {Vanadium treatment of type 2 diabetes: A view to the future},
	journal = {Journal of Inorganic Biochemistry},
	volume = {103},
	number = {4},
	year = {2009},
	note = {ISI Document Delivery No.: 429EUTimes Cited: 20Cited Reference Count: 41Thompson, Katherine H. Lichter, Jay LeBel, Carl Scaife, Michael C. McNeill, John H. Orvig, Chris6th International Vanadium SymposiumJUL 17-19, 2008Lisbon, PORTUGALSp. Iss. SI},
	month = {Apr},
	pages = {554-558},
	type = {Proceedings Paper},
	abstract = {3-Hydroxy-2-methyl-4-pryone and 2-ethyl 3-hydroxy-4-pyrone (maltol and ethyl maltol, respectively) have proven especially suitable a ligands for vanadyl tons, fit potential insulin enhancing agents for diabetes mellitus. Both bis(maltolato)oxovanadium(IV) (BMOV), and the ethylmaltol analog, bis(ethylmaltolato)oxovanadium(IV) (BEOV), have the desired intermediate stability for pro-drug use, and have undergone extensive pie-clinical testing for safety and efficacy. Pharmacokinetic evaluation indicates a pattern of biodistribution consistent with fairly rapid dissociation and uptake, binding to serum transferrin for systemic circulation and transport to tissues, with preferential uptake in bone. These bis-ligand oxovanadium(IV) (VOL2) compounds have a clear advantage over inorganic vanadyl sulfate in terms of bioavailability and pharmaceutical efficacy. BEOV has now completed Phase I and has advanced to Phase II clinical trials. In the Phase I trial, a ran-e of doses horn 10 mg, to 90 mg BEOV, given orally to non-diabetic volunteers, resulted in no adverse effects, all biochemical parameters remained within normal limits. In the Phase IIa trial, BEOV (AKP-020). 20 mg, daily for 28 clays, per os, in seven type 2 diabetic Subjects, was associated with reductions in fasting blood and glucose and \%HbA1c; improved responses to oral glucose tolerance testing, versus, the observed worsening of diabetic symptoms in the two placebo controls. (C) 2009 Elsevier Inc. All rights reserved.},
	keywords = {BIODISTRIBUTION, bis(ethylmaltolato)oxovanadium(IV), BIS(MALTOLATO)OXOVANADIUM(IV), CHEMISTRY, Diabetes mellitus, IN-VIVO, INSULIN SENSITIVITY, MALTOL, METAL-COMPLEXES, RATS, SERUM, SKELETAL-MUSCLE, SULFATE, VANADIUM},
	isbn = {0162-0134},
	url = {<Go to ISI>://000264904400011},
	author = {Thompson, K. H. and Lichter, J. and Lebel, C. and Scaife, M. C. and McNeill, J. H. and Orvig, Chris}
}
@article {1600,
	title = {Metal complexes in medicinal chemistry: new vistas and challenges in drug design},
	journal = {Dalton Transactions},
	number = {6},
	year = {2006},
	note = {ISI Document Delivery No.: 014YVTimes Cited: 60Cited Reference Count: 44},
	month = {Feb},
	pages = {761-764},
	type = {Article},
	abstract = {An overview is presented of selected metal-bases! pharmaceuticals, either diagnostic or therapeutic, with emphasis on specific attributes and in vivo interactions of these compounds relevant to their use in medicinal applications. Both the advantages and the challenges of this approach are outlined, with possibilities for future developments accentuated.},
	keywords = {AGENTS, BINDING CONSTANTS, BIS(MALTOLATO)OXOVANADIUM(IV), GLUCOSE, HUMAN-SERUM TRANSFERRIN, MODULATION, therapy, TRANSPORT},
	isbn = {1477-9226},
	url = {<Go to ISI>://000235520000001},
	author = {Thompson, K. H. and Orvig, Chris}
}
@article {1241,
	title = {Coordination chemistry and insulin-enhancing behavior of vanadium complexes with maltol C6H6O3 structural isomers},
	journal = {Inorganic Chemistry},
	volume = {44},
	number = {8},
	year = {2005},
	note = {ISI Document Delivery No.: 916GWTimes Cited: 19Cited Reference Count: 49},
	month = {Apr},
	pages = {2689-2697},
	type = {Article},
	abstract = {Syntheses of vanadium complexes using the naturally occurring ligands isomaltol (Hima) and allomaltol (Hama), as well as a newly synthesized, potentially tetradentate diaminodipyrone [H-2(en(ama)(2)], are reported. Complete characterization of the resulting compounds [trans-VO(ima)(2)(H2O), VO(ama)(2), V(ima)(3), V(ama)(3) and VO(en(ama)(2))], including X-ray crystallography analyses for trans-VO(ima)(2)(H2O) and V(ima)3, are presented herein. Potentiometric titrations (25 degrees C, / = 0.16 M NaCl) were used to measure stability constants in the V(IV)-Hima system; these data were compared to previous data collected on the V(IV)-L (L = Hma, Hama) systems. The in vivo efficacy of these compounds to lower the blood glucose levels of STZ-diabetic rats was tested; all but VO(en(ama)2) produced significant decreases in plasma glucose levels. The results were compared to those of the benchmark compound BMOV [VO(ma)(2), bis(maltolato)oxovanadium(IV)], a known insulin-enhancing agent.},
	keywords = {aluminum, BIS(MALTOLATO)OXOVANADIUM(IV), CRYSTAL-STRUCTURE, DIABETIC-RATS, ISOMALTOL, LIGANDS, REFINEMENT, SPECIATION, therapy, VANADATE},
	isbn = {0020-1669},
	url = {<Go to ISI>://000228374400019},
	author = {Saatchi, K. and Thompson, K. H. and Patrick, B. O. and Pink, M. and Yuen, V. G. and McNeill, J. H. and Orvig, Chris}
}
@article {1209,
	title = {Vanadium complexes with mixed O,S anionic ligands derived from maltol: Synthesis, characterization, and biological studies},
	journal = {Inorganic Chemistry},
	volume = {44},
	number = {8},
	year = {2005},
	note = {ISI Document Delivery No.: 916GWTimes Cited: 32Cited Reference Count: 45},
	month = {Apr},
	pages = {2678-2688},
	type = {Article},
	abstract = {Four mixed O,S binding bidentate ligand precursors derived from maltol (3-hydroxy-2-methyl-4-pyrone) have been chelated to vanadium to yield new bis(ligand)oxovanadium(IV) and tris(ligand)vanadium(III) complexes. The four ligand precursors include two pyranthiones, 3-hydroxy-2- m ethyl-4-pyranthione, commonly known as thiomaltol (Htma), and 2-ethyl-3-hydroxy-4-pyranthione, commonly known as ethylthiomaltol (Hetma), as well as two pyridinethiones, 3-hydroxy-2-methyl-4(H)-pyridinethione (Hmppt) and 3-hydroxy-1,2-dimethyi-4-pyridinethione (Hdppt). Vanadium complex formation was confirmed by elemental analysis, mass spectrometry, and IR and EPR (where possible) spectroscopies. The X-ray structure of oxobis(thiomaltolato)vanadium(IV),VO(tma)(2), was also determined; both cis and trans isomers were isolated in the same asymmetric unit. In both isomers, the two thiomaltolato ligands are arranged around the base of the square pyramid with the V=O linkage perpendicular; the vanadium atom is slightly displaced from the basal plane [V(1) = 0.656(3) angstrom, V(2) = 0.664(2) angstrom]. All of the new complexes were screened for insulin-enhancing effectiveness in streptozotocin-induced diabetes in rats, and VO(tma)2 was profiled metabolically for urinary vanadium and ligand clearance by GFAAS and ESIMS, respectively. The new vanadium complexes did not lower blood glucose levels acutely, possibly because of rapid dissociation and excretion.},
	keywords = {BIOCHEMISTRY, BIS(MALTOLATO)OXOVANADIUM(IV), COORDINATION CHEMISTRY, CRYSTAL-STRUCTURE, EPR, IN-VITRO, METAL, OXOVANADIUM(IV)},
	isbn = {0020-1669},
	url = {<Go to ISI>://000228374400018},
	author = {Monga, V. and Thompson, K. H. and Yuen, V. G. and Sharma, V. and Patrick, B. O. and McNeill, J. H. and Orvig, Chris}
}
@article {1209,
	title = {Vanadium complexes with mixed O,S anionic ligands derived from maltol: Synthesis, characterization, and biological studies},
	journal = {Inorganic Chemistry},
	volume = {44},
	number = {8},
	year = {2005},
	note = {ISI Document Delivery No.: 916GWTimes Cited: 32Cited Reference Count: 45},
	month = {Apr},
	pages = {2678-2688},
	type = {Article},
	abstract = {Four mixed O,S binding bidentate ligand precursors derived from maltol (3-hydroxy-2-methyl-4-pyrone) have been chelated to vanadium to yield new bis(ligand)oxovanadium(IV) and tris(ligand)vanadium(III) complexes. The four ligand precursors include two pyranthiones, 3-hydroxy-2- m ethyl-4-pyranthione, commonly known as thiomaltol (Htma), and 2-ethyl-3-hydroxy-4-pyranthione, commonly known as ethylthiomaltol (Hetma), as well as two pyridinethiones, 3-hydroxy-2-methyl-4(H)-pyridinethione (Hmppt) and 3-hydroxy-1,2-dimethyi-4-pyridinethione (Hdppt). Vanadium complex formation was confirmed by elemental analysis, mass spectrometry, and IR and EPR (where possible) spectroscopies. The X-ray structure of oxobis(thiomaltolato)vanadium(IV),VO(tma)(2), was also determined; both cis and trans isomers were isolated in the same asymmetric unit. In both isomers, the two thiomaltolato ligands are arranged around the base of the square pyramid with the V=O linkage perpendicular; the vanadium atom is slightly displaced from the basal plane [V(1) = 0.656(3) angstrom, V(2) = 0.664(2) angstrom]. All of the new complexes were screened for insulin-enhancing effectiveness in streptozotocin-induced diabetes in rats, and VO(tma)2 was profiled metabolically for urinary vanadium and ligand clearance by GFAAS and ESIMS, respectively. The new vanadium complexes did not lower blood glucose levels acutely, possibly because of rapid dissociation and excretion.},
	keywords = {BIOCHEMISTRY, BIS(MALTOLATO)OXOVANADIUM(IV), COORDINATION CHEMISTRY, CRYSTAL-STRUCTURE, EPR, IN-VITRO, METAL, OXOVANADIUM(IV)},
	isbn = {0020-1669},
	url = {<Go to ISI>://000228374400018},
	author = {Monga, V. and Thompson, K. H. and Yuen, V. G. and Sharma, V. and Patrick, B. O. and McNeill, J. H. and Orvig, Chris}
}
@article {1010,
	title = {Complementary inhibition of synoviocyte, smooth muscle cell or mouse lymphoma cell proliferation by a vanadyl curcumin complex compared to curcumin alone},
	journal = {Journal of Inorganic Biochemistry},
	volume = {98},
	number = {12},
	year = {2004},
	note = {ISI Document Delivery No.: 876VBTimes Cited: 20Cited Reference Count: 62},
	month = {Dec},
	pages = {2063-2070},
	type = {Article},
	abstract = {A novel vanadyl curcumin complex (VO(cur)2) has been synthesized and and its physicochemical properties characterized. Biological characterization included in vitro testing for anti-rheumatic activity in synoviocytes, angiogenesis inhibition in smooth muscle cells and anti-cancer potential in mouse lymphoma cells; as well as in vivo testing for hypoglycemic activity by oral gavage in streptozotocin (STZ)-diabetic rats. VO(cur)2 was more effective as an anti-cancer agent, compared to uncomplexed curcumin or vanadyl ion alone, was more than twice as effective as curcumin alone as an anti-arthritic agent, and was more than four times as effective as curcumin alone in inhibiting smooth muscle cell proliferation. In both acute and chronic screening tests, VO(cur)2 was ineffective as an insulin mimetic agent; however, it also proved to be exceptionally non-toxic, with no evidence of negative symptornatology during a month-long treatment period, at doses up to and including 2.0 mmol kg(-1) day(-1). (C) 2004 Elsevier Inc. All rights reserved.},
	keywords = {antioxidant, apoptosis, arthritis lymphoma, BIS(MALTOLATO)OXOVANADIUM(IV), CELLS, COMPLEX, COORDINATION, curcurnin, DIABETIC-RATS, DIFERULOYL METHANE CURCUMIN, FREE-RADICALS, INDUCED LIPID-PEROXIDATION, INSULIN MIMICS, LEUKEMIA HL-60, METAL-IONS, OXIDATIVE STRESS, vanadyl ion},
	isbn = {0162-0134},
	url = {<Go to ISI>://000225525200010},
	author = {Thompson, K. H. and Bohmerle, K. and Polishchuk, E. and Martins, C. and Toleikis, P. and Tse, J. and Yuen, V. and McNeill, J. H. and Orvig, Chris}
}
@article {742,
	title = {Vanadyl-thiazolidinedione combination agents for diabetes therapy},
	journal = {Bioconjugate Chemistry},
	volume = {14},
	number = {1},
	year = {2003},
	note = {ISI Document Delivery No.: 637YYTimes Cited: 23Cited Reference Count: 42},
	month = {Jan-Feb},
	pages = {212-221},
	type = {Article},
	abstract = {A series of vanadium compounds, chelated by ligands containing a thiazolidinedione moiety as an additional insulin-enhancing component, were produced in this study to create potentially synergistic compounds. A set of four bifunctional ligand precursors were synthesized: (+/-)-5-4-[(5-hydroxy-4-oxo-4H-pyran-2-ylmethyl)amino]benzylthiazolidi ne-2,4-dione (HL1), (+/-)-5-4-[5-hydroxy-1-methyl-4-oxo-1,4-dihydro-pyridin-2-ylmethyl)amin o]benzylthiazolidine-2,4-dione (HL2) 5-[4-(5-hydroxy-4-oxo-4H-pyran-2-ylmethoxy)benzylidenelthiazolidine-2,4- dione (HL1), and (+/-)-5-4-(5-hydroxy-4-oxo-4H-pyran-2-ylmethoxy)benzyl]thiazolidine-2,4 -dione (HL4), each containing a metal chelating portion as well as a thiazolidinedione moiety. From this set of ligand precursors, air-stable VO(L-1)(2), VO(L-3)(2), and VO(L-4)(2) were prepared. The four ligand precursors and three complexes were tested for insulin-enhancing potential in STZ-diabetic rats and compared to rosiglitazone and BMOV, respectively. Both the ligand precursors HL1 and HL3 showed enhanced activity compared with that of rosiglitazone. The complex VO(L-3)(2) showed the most efficacious hypoglycemic effects in this study; however, neither additive nor synergistic effects were observed using this acute animal model.},
	keywords = {AGENT, ANTIHYPERGLYCEMIC, BIOLOGICAL-ACTIVITY, BIS(MALTOLATO)OXOVANADIUM(IV), BLOOD-GLUCOSE, COMPLEXES, DERIVATIVES, GLUCOSE-LOWERING PROPERTIES, INSULIN MIMETIC AGENT, RAT ADIPOCYTES, TROGLITAZONE},
	isbn = {1043-1802},
	url = {<Go to ISI>://000180542400025},
	author = {Storr, T. and Mitchell, D. and Buglyo, P. and Thompson, K. H. and Yuen, V. G. and McNeill, J. H. and Orvig, Chris}
}
@article {524,
	title = {Influence of chelation and oxidation state on vanadium bioavailability, and their effects on tissue concentrations of zinc, copper, and iron},
	journal = {Biological Trace Element Research},
	volume = {86},
	number = {1},
	year = {2002},
	note = {ISI Document Delivery No.: 541ZTTimes Cited: 27Cited Reference Count: 45},
	month = {Apr},
	pages = {31-44},
	type = {Article},
	abstract = {Today, vanadium compounds are frequently included in nutritional supplements and are also being developed for therapeutic use in diabetes mellitus. Previously, tissue uptake of vanadium from bis(maltolato)oxovanadium(IV) (BMOV) was shown to be increased compared to its uptake from vanadyl sulfate (VS). Our primary objective was to test the hypothesis that complexation increases vanadium uptake and that this effect is independent of oxidation state. A secondary objective was to compare the effects of vanadium complexation and oxidation state on tissue iron, copper, and zinc. Wistar rats were fed either ammonium metavanadate (AMV), VS, or BMOV (1.2 mM each in the drinking water). Tissue uptake of V following 12 wk of BMOV or AMV was higher than that from VS (p < 0.05). BMOV led to decreased tissue Zn and increased bone Fe content. The same three compounds were compared in a cellular model of absorption (Caco-2 cells). Vanadium uptake from VS was higher than that from BMOV or AMV at 10 min, but from BMOV (250 \&mu;M only, 60 min), uptake was far greater than from AMV or VS. These results show that neither complexation nor oxidation state alone are adequate predictors of relative absorption, tissue accumulation, or trace element interactions.},
	keywords = {ABSORPTION, BIS(MALTOLATO)OXOVANADIUM(IV), bone, CACO-2, Caco-2 cells, COMPLEXES, DIABETIC RATS, GLUCOSE-METABOLISM, IN-VITRO, INSULIN, kidney, ORTHO-VANADATE, skeletal muscle, SULFATE, VANADIUM, zinc},
	isbn = {0163-4984},
	url = {<Go to ISI>://000175018100004},
	author = {Thompson, K. H. and Tsukada, Y. and Xu, Z. M. and Battell, M. and McNeill, J. H. and Orvig, Chris}
}
@article {509,
	title = {Synthesis and solution studies of the complexes of pyrone analogue ligands with vanadium(IV) and vanadium(V)},
	journal = {Inorganica Chimica Acta},
	volume = {339},
	year = {2002},
	note = {ISI Document Delivery No.: 616BDTimes Cited: 8Cited Reference Count: 16},
	month = {Nov},
	pages = {393-399},
	type = {Article},
	abstract = {A new potentially tetradentate chelator N,N{\textquoteright}-bis(3-hydroxy-6-methyl-2-methylene-4-pyrone)ethylenediamine (H-2(en(ama)(2))), has been synthesized and its protonation constants, as well as those of two other 3-hydroxy-4-pyrone ligands (allomaltol (Hama) and methylmaltol (Hmma)) determined potentiometrically at 25 degreesC and 0.16 M NaCl: pK(a1) = 3.67+/-0.07, pK(a2) = 5.82+/-0.07, pK(a3) = 7.96+/-0.04, pK(a4) = 8.77+/-0.03 for [H-4(en(ama)(2))](2+), pK(a) = 8.04+/-0.02 for Hama and pK(a) = 8.82+/-0.02 for Hmma. Potentiometric pH titrations were also used to measure the stability constants of these ligands with V(IV) and V(V) and to study the structures of the complexes of (en(ama)(2))(2-) in aqueous solution. H-1 NMR was used to assign the protonation constant values to the different protons in H-2(en(ama)(2)). A pM versus pH plot confirmed that H-2(en(ama)(2)) has much stronger complexation than its bidentate analogues, in the same pH range. (C) 2002 Elsevier Science B.V. All rights reserved.},
	keywords = {AQUEOUS-SOLUTION, BIS(MALTOLATO)OXOVANADIUM(IV), GLUCOSE, insulin drugs, ION-COORDINATING PROPERTIES, potentiometry, stability constants, vanadium complexes},
	isbn = {0020-1693},
	url = {<Go to ISI>://000179281100048},
	author = {Song, B. and Saatchi, K. and Rawji, G. H. and Orvig, Chris}
}
@article {5148,
	title = {Insulin-enhancing vanadium(III) complexes},
	journal = {Inorganic Chemistry},
	volume = {40},
	number = {18},
	year = {2001},
	note = {ISI Document Delivery No.: 466JNTimes Cited: 67Cited Reference Count: 54},
	month = {Aug},
	pages = {4686-4690},
	type = {Article},
	abstract = {Simple, high-yield, large-scale syntheses of the V(III) complexes tris(maltolato)vanadium(III), V(ma)(3), tris-(ethyhmaltolato)vanadium(HI), V(ema)(3), tris(kojato)vanadium(III) monchydrate, V(koj)(3).H2O, and tris(1,2-dimethyl-3-hydroxy-4-pyridinonato)vanadium(III) dodecahydrate, V(dpp)(3). 12H(2)O, are described; the characterization of these complexes by various methods and, in the case of V(dpp)(3). 12H(2)O, by an X-ray crystal structure determination, is reported. The ability of these complexes to normalize glucose levels in the STZ-diabetic rat model has been examined and compared with that of the benchmark compound BMOV (bis(maltolato)oxovanadium(IV)), an established insulin-enhancing agent.},
	keywords = {AGENT, aluminum, BIS(MALTOLATO)OXOVANADIUM(IV), CHELATE COMPLEXES, COORDINATION CHEMISTRY, CRYSTAL-STRUCTURE, DIABETIC RATS, gallium, GLUCOSE, LIGANDS, MIMETIC},
	isbn = {0020-1669},
	url = {<Go to ISI>://000170642600028},
	author = {Melchior, M. and Rettig, S. J. and Liboiron, B. D. and Thompson, K. H. and Yuen, V. G. and McNeill, J. H. and Orvig, Chris}
}
@article {4616,
	title = {Vanadium complexes as insulin mimetic agents: Coordination chemistry and in vivo studies of oxovanadium(IV) and dioxovanadate(V) complexes formed from naturally occurring chelating oxazolinate, thiazolinate, or picolinate units},
	journal = {Inorganic Chemistry},
	volume = {38},
	number = {10},
	year = {1999},
	note = {ISI Document Delivery No.: 199BHTimes Cited: 72Cited Reference Count: 34},
	month = {May},
	pages = {2288-2293},
	type = {Article},
	abstract = {{The synthesis and characterization of four complexes containing naturally occurring binding groups are reported: VO(pic)(2). H2O (Hpic = picolinic or pyridine-2-carboxylic acid), NH4[VO2(pic)(2)]. 2H(2)O, VO(oz)(2) (Hoz = 2-(2{\textquoteright}- hydroxyphenyl)-2-oxazoline), and VO(thoz)(2) (Hthoz = 2-(2{\textquoteright}-hydroxyphenyl)-2-thiazoline). The X-ray structures of [NH4[VO2(pic)(2)]. 2H(2)O, VO(oz)(2), and VO(thoz)(2) have been determined. Crystals of NH4[VO2(pic)(2)]. 2H(2)O (C12H12N3O6V . 2H(2)O) are monoclinic, space group Cc, a 10.347(2) Angstrom},
	keywords = {BIS(MALTOLATO)OXOVANADIUM(IV), BMOV, CRYSTAL-STRUCTURE, DIABETIC RATS, GLUCOSE, NMR, SIDEROPHORE, SULFATE, SYSTEM, VANADATE},
	isbn = {0020-1669},
	url = {<Go to ISI>://000080459200009},
	author = {Melchior, M. and Thompson, K. H. and Jong, J. M. and Rettig, S. J. and Shuter, E. and Yuen, V. G. and Zhou, Y. and McNeill, J. H. and Orvig, Chris}
}
@article {4706,
	title = {Vanadyl-biguanide complexes as potential synergistic insulin mimics},
	journal = {Journal of Inorganic Biochemistry},
	volume = {76},
	number = {3-4},
	year = {1999},
	note = {ISI Document Delivery No.: 262ZHTimes Cited: 65Cited Reference Count: 27},
	month = {Sep},
	pages = {251-257},
	type = {Article},
	abstract = {Vanadium has well-documented blood-glucose-lowering properties both in vitro and in vivo. The design of new oxovanadium(IV) coordination compounds, intended for use as insulin-enhancing agents in the treatment of diabetes mellitus, can potentially benefit from a synergistic approach, in which the whole complex has more than an additive effect from its component parts. Biguanides, most importantly metformin, are oral hypoglycemic agents used today to treat type 2 diabetes mellitus. In this study, biguanide, metformin, and phenformin, all biguanides, were coordinated to oxovanadium(IV) to form potential insulin-enhancing compounds. Highly colored, air-stable, bis(biguanidato)oxovanadium(IV), [VO(big)(2)], bis(N{\textquoteright},N{\textquoteright}-dimethylbiguanidato)oxovanadium(IV) [VO(metf)(2)], and bis(beta-phenethyl-biguanidato)oxovanadium(IV), [VO(phenf)(2)], were prepared. Solvation with dimethylsulfoxide occurred with VO(metf)(2) to form a six-coordinate complex. Precursor ligands and oxovanadium(IV) coordination complexes were characterized by infrared spectroscopy, mass spectrometry, elemental analyses, magnetic susceptibility, and, where appropriate, H-1 NMR spectroscopy. Biological testing with VO(metf)(2), a representative compound, for insulin-enhancing potential included acute (72 h) administration, both by intraperitoneal (i.p.) injection and by oral gavage (p.o,) in streptozotocin (STZ)-diabetic rats. VO(metf)(2) administration resulted in significant blood-glucose lowering at doses of 0.12 mmol kg(-1) i.p. and 0.60 mmol kg(-1) p.o. (previously established as ED50 doses for organically chelated oxovanadium(IV) complexes); however, no positive associative effects due to the presence of biguanide in the complex were apparent. (C) 1999 Elsevier Science Inc. All rights reserved.},
	keywords = {biguanide, BIS(MALTOLATO)OXOVANADIUM(IV), BMOV, coordination complex, GLUCOSE-LOWERING PROPERTIES, insulin mimic, MECHANISM, METFORMIN, MIMETIC AGENT, MUSCLE, RATS, VANADIUM},
	isbn = {0162-0134},
	url = {<Go to ISI>://000084097800010},
	author = {Woo, L. C. Y. and Yuen, V. G. and Thompson, K. H. and McNeill, J. H. and Orvig, Chris}
}
@article {4399,
	title = {Kinetic analysis and comparison of uptake, distribution, and excretion of V-48-labeled compounds in rats},
	journal = {Journal of Applied Physiology},
	volume = {84},
	number = {2},
	year = {1998},
	note = {ISI Document Delivery No.: YU964Times Cited: 63Cited Reference Count: 43},
	month = {Feb},
	pages = {569-575},
	type = {Article},
	abstract = {Vanadium has been found to be orally active in lowering plasma glucose levels; thus it provides a potential treatment for diabetes mellitus. Bis(maltolato)oxovanadium(rv) (BMOV) is a well-characterized organovanadium compound that has been shown in preliminary studies to have a potentially useful absorption profile. Tissue distributions of BMOV compared with those of vanadyl sulfate (VS) were studied in Wistar rats by using V-48 as a tracer. In this study, the compounds were administered in carrier-added forms by either oral gavage or intraperitoneal injection. Data analyzed by a compartmental model, by using simulation, analysis, and modeling (i.e., SAAM II) software, showed a pattern of increased tissue uptake with use of V-48-BMOV compared with (VS)-V-48. The highest V-48 concentrations at 24 h after gavage were in bone, followed by kidney and liver. Most ingested V-48 was eliminated unabsorbed by fecal excretion. On average, V-48 concentrations in bone, kidney, and liver 24 h after oral administration of V-48-BMOV were two to three times higher than those of (VS)-V-48, which is consistent with the increased glucose-lowering potency of BMOV in acute glucose lowering compared with VS.},
	keywords = {ADIPOCYTES, analysis, and modeling, BIS(MALTOLATO)OXOVANADIUM(IV), compartmental modeling, diabetes, DISSOCIATION, FERRIC MALTOL, GLUCOSE, INDUCED DIABETIC RATS, INSULIN, insulin mimetic, METABOLISM, MOLYBDENUM, SIMULATION, SMALL-INTESTINE, Software, VANADIUM, VANADYL SULFATE},
	isbn = {8750-7587},
	url = {<Go to ISI>://000071774300025},
	author = {Setyawati, I. A. and Thompson, K. H. and Yuen, V. G. and Sun, Y. and Battell, M. and Lyster, D. M. and Vo, C. and Ruth, T. J. and Zeisler, S. and McNeill, J. H. and Orvig, Chris}
}
@article {3578,
	title = {COMPARISON OF THE GLUCOSE-LOWERING PROPERTIES OF VANADYL SULFATE AND BIS(MALTOLATO)OXOVANADIUM(IV) FOLLOWING ACUTE AND CHRONIC ADMINISTRATION},
	journal = {Canadian Journal of Physiology and Pharmacology},
	volume = {73},
	number = {1},
	year = {1995},
	note = {ISI Document Delivery No.: QN264Times Cited: 71Cited Reference Count: 31},
	month = {Jan},
	pages = {55-64},
	type = {Article},
	abstract = {Numerous studies, bath in vitro and in vivo, have demonstrated the insulin-mimetic properties of vanadium. Chronic oral administration of inorganic and organic compounds of both vanadium(IV) and vanadium(V) reduced plasma glucose levels and restored plasma lipid levels in streptozotocin-diabetic rats. We investigated the acute effects of both vanadyl sulfate and bis(maltolato)oxovanadium(IV) (BMOV), an organic vanadium compound, on plasma glucose levels by several routes of administration. Previous studies have shown that chronic administration of vanadyl sulfate has resulted in a sustained euglycemia following withdrawal of the drug. This effect was not observed following the chronic administration of BMOV; therefore, we investigated the effect of increasing the concentration of BMOV on the production of a sustained euglycemic response. An acute plasma glucose lowering effect was obtained with both vanadyl sulfate and BMOV when administered as a single dose by either oral gavage or intraperitoneal injection. In those animals that responded to vanadium treatment, plasma glucose levels were within the normal range within 2 to 6 h when given by i.p. injection or within 4 to 8 h when given by oral gavage. BMOV-treated rats that responded to treatment maintained the euglycemic effect for extended periods, ranging from 1 to 14 weeks following administration. However, vanadyl sulfate treated rats reverted to hyperglycemia within 12 to 24 h, depending on the route of administration. Intravenous administration of BMOV was effective in lowering plasma glucose levels only when administered by continuous infusion. An oral dose - response curve showed that BMOV was 2 to 3 times as potent as vanadyl sulfate. This difference in potency was observed with both oral and intraperitoneal administration, which suggests that the increase in potency with BMOV cannot be totally attributed to increased gastrointestinal absorption. Organic chelation of vanadium may facilitate uptake into vanadium-sensitive tissues. Chronic oral administration of higher concentrations of BMOV did not result in a sustained reduction in plasma glucose following withdrawal of the drug. All diabetic rats eventually responded to increased concentrations of BMOV with a restoration of plasma glucose levels to normal values; however, reversion to the hyperglycemic state occurred within 2 days of withdrawal of treatment. Chronic oral administration of BMOV did not produce a sustained euglycemic effect following withdrawal, but acute administrations of the compound by either oral gavage or intraperitoneal injection did produce a long-term reduction in plasma glucose levels. Rats treated chronically with vanadyl sulfate remained euglycemic even after the drug was withdrawn. However, acute treatment produced only a transient euglycemia.},
	keywords = {ACUTE, BIS(MALTOLATO)OXOVANADIUM(IV), BLOOD-GLUCOSE, DOSE RESPONSE, GAVAGE, HOMEOSTASIS, IMPROVEMENT, INDUCED DIABETIC RATS, INSULIN, STREPTOZOTOCIN DIABETIC, SULFATE, VANADYL},
	isbn = {0008-4212},
	url = {<Go to ISI>://A1995QN26400008},
	author = {Yuen, V. G. and Orvig, Chris and McNeill, J. H.}
}
@article {3447,
	title = {Increased potency of vanadium using organic ligands},
	journal = {Molecular and Cellular Biochemistry},
	volume = {153},
	number = {1-2},
	year = {1995},
	note = {ISI Document Delivery No.: TM620Times Cited: 45Cited Reference Count: 46Vanadium SymposiumJUL 29-31, 1994MONTREAL, CANADACanadian Diabet Assoc, Fonds Rech Sante Quebec, Juvenile Diabet Fdn Canada, Marion Merrell Dow Canada, McGill Univ, Med Res Council Canada, Medisense Canada Inc, Merck Frosst, Canada Inc, Miles Canada Inc},
	month = {Dec},
	pages = {175-180},
	type = {Proceedings Paper},
	abstract = {The in vivo glucose lowering effect of orally administered inorganic vanadium compounds in diabetes was first reported in our laboratory in 1985. While both vanadate and vanadyl forms of vanadium are orally active, they are still not well absorbed. We have synthesized several organic vanadium compounds and one compound, bis(maltolato)oxovanadium(lv) or BMOV, has been extensively investigated. BMOV proved effective in lowering plasma glucose and lipids in STZ-diabetic: rats when administered in drinking water over a 25 week period. The maintenance dose (0.18 mmol/kg/day) was approximately 50\% of that required for vanadyl sulfate (VS). Secondary complications of diabetes were prevented by BMOV and no marked toxicity was noted. Oral gavage of STZ-diabetic rats with BMOV also reduced blood glucose levels. The ED(50) for BMOV was 0.5 mmol/kg, while for VS the estimated ED(50) was 0.9 mmol/kg. BMOV was also effective by the intraperitoneal route in STZ-diabetic rats. The ED(50) was 0.08 mmol/kg compared to 0.22 mmol/kg for VS. Some animals treated p.o. or i.p. remained euglycemic for up to 14 weeks. An i.v. infusion of BMOV of 0.05 mmol/kg over a 30 min period reduced plasma glucose levels by 50\% while VS was not effective.},
	keywords = {ADIPOCYTES, BIS(MALTOLATO)OXOVANADIUM(IV), diabetes, DIABETIC, GLUCOSE, HYPERTENSION, IMPROVEMENT, INSULIN ACTION, insulin-mimetic, RATS, RECEPTOR TYROSINE KINASE, resistance, SPONTANEOUSLY HYPERTENSIVE RATS, VANADATE, VANADIUM},
	isbn = {0300-8177},
	url = {<Go to ISI>://A1995TM62000024},
	author = {McNeill, J. H. and Yuen, V. G. and Dai, S. T. and Orvig, Chris}
}
@article {2940,
	title = {GLUCOSE-LOWERING EFFECTS OF A NEW ORGANIC VANADIUM COMPLEX, BIS(MALTOLATO)OXOVANADIUM(IV)},
	journal = {Canadian Journal of Physiology and Pharmacology},
	volume = {71},
	number = {3-4},
	year = {1993},
	note = {ISI Document Delivery No.: LN775Times Cited: 84Cited Reference Count: 39},
	month = {Mar-Apr},
	pages = {263-269},
	type = {Article},
	abstract = {Inorganic vanadium has been shown, both in vivo and in vitro, to have insulin-mimetic properties. A new organic vanadium complex, bis(maltolato)oxovanadium(IV) (BMOV), was developed to increase the absorption of vanadium from the gastrointestinal tract, thereby reducing the dose of vanadium necessary to produce glucose-lowering effects. BMOV was administered in the drinking water for 25 weeks to control and streptozotocin-induced diabetic, male Wistar rats. BMOV treatment produced a stable euglycemic state in 70\% of diabetic treated animals. The other 30\% of the diabetic treated animals demonstrated fluctuations in glucose control over the entire study period. The initial effective dose of BMOV was 0.45 mmol/kg, which decreased to an effective maintenance dose of 0. 18 mmol/kg, significantly lower than the dose of inorganic vanadium salts used in previous studies. BMOV treatment did significantly reduce fluid consumption levels in control treated animals after 10 weeks of therapy; however, the food consumption for control treated animals was only intermittently lower than that for controls. Plasma cholesterol and triglyceride levels were normalized with BMOV treatment for all diabetic treated animals, without a concomitant increase in plasma insulin levels. An oral glucose tolerance test demonstrated that glucose homeostasis in control-treated animals occurred at significantly lower plasma insulin levels than in control animals. BMOV effectively produced the glucose-lowering effects at significantly lower dose than previously used for inorganic vanadium salts, without any overt signs of toxicity.},
	keywords = {ACTIVATION, ADIPOCYTES, BIS(MALTOLATO)OXOVANADIUM(IV), BLOOD-GLUCOSE, DIABETES TREATMENT, DIABETIC RATS, GLYCOLYSIS, INSULIN, SENSITIVITY, SKELETAL-MUSCLE, STIMULATION, streptozotocin-induced diabetes, VANADATE},
	isbn = {0008-4212},
	url = {<Go to ISI>://A1993LN77500013},
	author = {Yuen, V. G. and Orvig, Chris and McNeill, J. H.}
}
@article {2941,
	title = {IMPROVEMENT IN CARDIAC DYSFUNCTION IN STREPTOZOTOCIN-INDUCED DIABETIC RATS FOLLOWING CHRONIC ORAL-ADMINISTRATION OF BIS(MALTOLATO)OXOVANADIUM(IV)},
	journal = {Canadian Journal of Physiology and Pharmacology},
	volume = {71},
	number = {3-4},
	year = {1993},
	note = {ISI Document Delivery No.: LN775Times Cited: 70Cited Reference Count: 40},
	month = {Mar-Apr},
	pages = {270-276},
	type = {Article},
	abstract = {Decreased cardiac function in streptozotocin-diabetic rats has been used as a model of diabetes-induced cardiomyopathy, which is a secondary complication in diabetic patients. The present study was designed to evaluate the therapeutic effect of a new organic vanadium complex, bis(maltolato)oxovanadium(IV), (BMOV), in improving heart function in streptozotocin-diabetic rats. There were four groups of male, Wistar rats: control (C), control treated (CT), diabetic (D), and diabetic treated (DT). Treatment consisted of BMOV, 0.5 mg/mL (1.8 mM) for the first 3 weeks and 0.75 mg/mL (2.4 mM) for the next 22 weeks, in the drinking water of rats allowed ad libitum access to food and water. BMOV lowered blood glucose to < 9 mM in 70\% of DT animals without any increase in plasma insulin levels, and mean blood glucose and plasma lipid levels were significantly lower in DT vs. D rats. Tissue vanadium levels were measured in plasma, bone, kidney, liver, muscle, and fat of BMOV-treated rats. Plasma vanadium levels averaged 0.84 +/- 0.07 mug/mL (16.8 muM) in CT rats and 0.76 +/-0.05 mug/mL (15.2 muM) in DT animals. The highest vanadium levels at termination of this chronic feeding study were in bone, 18.3 +/- 3.0 mug/g (0.37 mumol/g) in CT and 26.4 +/- 2.6 mug/g (0.53 mumol/g) in DT rats, with intermediate levels in kidney and liver, and low, but detectable levels in muscle and fat. There were no deaths in either the CT or DT group, and no overt signs of vanadium toxicity were present. Tissue vanadium levels were not correlated with die glucose-lowering effect. Isolated working heart parameters of left ventricular developed pressure (LVDP) and rate of pressure development (+dP/dT, and -dP/dT) indicated that BMOV treatment resulted in significant correction of the heart dysfunction associated with streptozotocin-induced diabetes in rat.},
	keywords = {ACTIVATION, BIS(MALTOLATO)OXOVANADIUM(IV), BLOOD-GLUCOSE, diabetes, GLUCOSE-HOMEOSTASIS, INSULIN, MYOCARDIAL DYSFUNCTION, STREPTOZOTOCIN, SULFATE, VANADATE TREATMENT, VANADIUM},
	isbn = {0008-4212},
	url = {<Go to ISI>://A1993LN77500014},
	author = {Yuen, V. G. and Orvig, Chris and Thompson, K. H. and McNeill, J. H.}
}
