Synthesis of novel 3,7-substituted-2-(3',4'-dihydroxyphenyl)flavones with improved antioxidant activity

F.A.A. van Acker, G.J. Hageman, G.R.M.M. Haenen, W.J.F. van der Vijgh, A. Bast, W.M.P.B. Menge

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Abstract

A series of 3,7-disubstituted-2-(3',4'-dihydroxyphenyl)flavones was synthesized as potential cardioprotective agents in doxorubicin antitumor therapy. The influence of substituents on the 3 and 7 positions of the flavone nucleus on radical scavenging and antioxidant properties was explored to improve the antioxidant activity of our lead compound monoHER. In the TEAC assay most compounds had a similar potency (3.5-5 times as potent; as trolox), but in the LPO assay IC50 values ranged from 0.2 to 37 mu M. In general, the 3-substituted flavones (9a-j) were the most potent compounds in the LPO assay. The number of hydroxyl groups is not the only prerequisite for antioxidant activity. Substitution in ring A of the flavonoid is not necessary for high activity, but the presence of a 7-OH group significantly modifies the antioxidant activity. The compounds are good antioxidants, which makes it interesting to evaluate them as cardioprotective agents.
Original languageEnglish
Pages (from-to)3752-3760
Number of pages9
JournalJournal of Medicinal Chemistry
Volume43
DOIs
Publication statusPublished - 1 Jan 2000

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