@article {2628,
	title = {Glycosylated tetrahydrosalens as multifunctional molecules for Alzheimer{\textquoteright}s therapy},
	journal = {Dalton Transactions},
	number = {16},
	year = {2009},
	note = {ISI Document Delivery No.: 430GYTimes Cited: 8Cited Reference Count: 65Storr, Tim Scott, Lauren E. Bowen, Meryn L. Green, David E. Thompson, Katherine H. Schugar, Harvey J. Orvig, Chris},
	pages = {3034-3043},
	type = {Article},
	abstract = {The tetrahydrosalens N,N{\textquoteright}-bis(2-hydroxybenzyl)-ethane-1,2-diamine (H2L1), N, N{\textquoteright}-bis(2-hydroxybenzyl)-(-)-1,2-cyclohexane-(1R, 2R)-diamine (H2L2), N,N{\textquoteright}-bis(2-hydroxybenzyl)-N,N{\textquoteright}-dimethyl-ethane-1,2-diamine (H2L3), N,N{\textquoteright}-bis(2-hydroxybenzyl)-N,N{\textquoteright}-dibenzyl-ethane-1,2diamine (H2L4), and N,N{\textquoteright}-bis(2-(4-tert-butyl) hydroxybenzyl)-ethane-1,2-diamine (H2L5), as well as their prodrug glycosylated forms, GL(1-5), have been prepared and evaluated in vitro for their potential use as Alzheimer{\textquoteright}s disease (AD) therapeutics. Dysfunctional interactions of metal ions, especially those of Cu, Zn, and Fe, with the amyloid-beta (A beta) peptide are hypothesised to play an important role in the aetiology of AD, and disruption of these aberrant metal-peptide interactions via chelation therapy holds considerable promise as a therapeutic strategy. Tetrahydrosalens such as H2L1-5 have a significant affinity for metal ions, and thus should be able to compete with the A beta peptide for Cu, Zn, and Fe in the brain. This activity was assayed in vitro via a turbidity assay; H2L1 and H2L3 were found to attenuate A beta(1-40) aggregation after exposure to Cu2+ and Zn2+. In addition, H2L1-5 were determined to be potent antioxidants on the basis of an in vitro antioxidant assay. GL(1-5) were prepared as metal binding prodrugs; glycosylation is intended to prevent systemic metal binding, improve solubility, and enhance brain uptake. Enzymatic (beta-glucosidase) deprotection of the carbohydrate moieties was facile, with the exception of GL(4), demonstrating the general feasibility of this prodrug approach. Finally, a representative prodrug, GL(3), was determined to be non-toxic over a large concentration range in a cell viability assay.},
	keywords = {A-BETA, ACTIVITY, antioxidant, COMPLEXES, DISEASE, HYDROGEN-PEROXIDE, IN-VITRO, NEURODEGENERATIVE DISORDERS, OXIDATIVE STRESS, TRANSGENIC MICE, zinc},
	isbn = {1477-9226},
	url = {<Go to ISI>://000264978300018},
	author = {Storr, T. and Scott, L. E. and Bowen, M. L. and Green, D. E. and Thompson, K. H. and Schugar, H. J. and Orvig, Chris}
}
@article {1011,
	title = {Comparison of anti-hyperglycemic effect amongst vanadium, molybdenum and other metal maltol complexes},
	journal = {Journal of Inorganic Biochemistry},
	volume = {98},
	number = {5},
	year = {2004},
	note = {ISI Document Delivery No.: 824HVTimes Cited: 37Cited Reference Count: 7411th International Conference on Biological Inorganic ChemistryJUL 19-23, 2003Cairns, AUSTRALIA},
	month = {May},
	pages = {683-690},
	type = {Proceedings Paper},
	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 [MoO2](2+), Co(II), Cu(II), Cr(III), and Zn(II), only [MoO2](2+) and Co(II) showed any hypoglycemic activity at the ED50 dose for bis(maltolato)oxovanadium(IV), 0.6 mmol kg(-1) by oral gavage in streptozotocin (STZ)-diabetic rats within 72 It of administration of compound. (C) 2004 Elsevier Inc. All rights reserved.},
	keywords = {ABSORPTION, CHROMIUM, cobalt, COORDINATION MODE, copper, DEPENDENT DIABETES-MELLITUS, GLUCOSE-METABOLISM, IN-VIVO, INSULIN, LIPID-METABOLISM, MOLYBDENUM, RATS, VANADIUM, zinc, ZINC SUPPLEMENTATION},
	isbn = {0162-0134},
	url = {<Go to ISI>://000221678300004},
	author = {Thompson, K. H. and Chiles, J. and Yuen, V. G. and Tse, J. 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}
}
