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 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 IC(50) values ranged from 0.2 to 37 microM. 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.
van Acker
F A
FA
Department of Medical Oncology, University Hospital Vrije Universiteit, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. f.vanacker@azvu.nl
Hageman
J A
JA
Haenen
G R
GR
van Der Vijgh
W J
WJ
Bast
A
A
Menge
W M
WM
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D005419:Flavonoids; D016166:Free Radical Scavengers