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

A series of 3,7-disubstituted-2-(3',4'-dihydroxyphenyl)flavones was synthes ized as potential cardioprotective agents in doxorubicin antitumor therapy. The influence of substituents on the 3 and 7 positions of the flavone nucl eus on radical scavenging and antioxidant properties was explored to improv e 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), bu t 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 ass ay. The number of hydroxyl groups is not the only prerequisite for antioxid ant 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 i nteresting to evaluate them as cardioprotective agents.