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.