@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}
}
