Chemical syntheses of Trolox conjugates which protect human ventricular myocytes against in situ-generated oxyradicals.
Synthetic conjugates of the antioxidant Trolox (6-hydroxy-2,5,7,8-tetramethyl chroman-2-carboxylic acid) have been prepared by coupling it with 1-ethyl-3-(3-dimethyl-amino-propyl) carbodiimide hydrochloride either to p-aminophenyl-beta-D-lactopyranoside, or to higher molecular weight ligands such as dextran and polylysine. Compared to Trolox and on a mole to mole basis, dextran-Trolox is almost equally active, while lactosylphenyl- and polylysine-Trolox conjugates are distinctly more active in preventing the damage on human ventricular myocytes by oxyradicals generated from xanthine oxidase-hypoxanthine. Listed in order of decreasing cytoprotective activity, they are: lactosylphenyl-Trolox >> polylysine-Trolox > Trolox > dextran-Trolox. Thus, Trolox can be chemically modified by coupling it to one of a number of ligands and, in some cases, with resultant increases in its ability to protect human ventricular myocytes from oxyradical damage.
Zielenski
J
J
Department of Clinical Biochemistry, University of Toronto, Ontario, Canada.
Wu
T W
TW
Fung
K P
KP
Zeng
L H
LH
Li
R K
RK
Mickle
D A
DA
Wu
J
J
D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003911:Dextrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D011107:Polylysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014969:Xanthine Oxidase / Q000187:drug effects
D000975:Antioxidants; D002839:Chromans; D003911:Dextrans; D016166:Free Radical Scavengers; D006027:Glycosides; C087242:dextran-trolox conjugate; C087241:polylysine-trolox conjugate; C073455:lactosylphenyl-trolox; D011107:Polylysine; D014969:Xanthine Oxidase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid