Inhibition of LDL oxidation by flavonoids in relation to their structure and calculated enthalpy.
Twenty flavonoid compounds of five different subclasses were selected, and the relationship of their structure to the inhibition of low-density lipoprotein (LDL) oxidation in vitro was investigated. The most effective inhibitors, by either copper ion or 2,2'-azobis (2-amidino-propane) dihydrochloride (AAPH) induction, were flavonols and/or flavonoids with two adjacent hydroxyl groups at ring B. In the presence of the later catechol group, the contribution of the double bond and the carbonyl group at ring C was negligible. Isoflavonoids were more effective inhibitors than other flavonoid subclasses with similar structure. Substituting ring B with hydroxyl group(s) at 2' position resulted in a significantly higher inhibitory effect than by substituting ring A or ring B at other positions. The type of LDL inducer had no effect in flavonoids with catechol structure. Calculated heat of formation data (deltadeltaH(f)) revealed that the donation of a hydrogen atom from position 3 was the most likely result, followed by that of a hydroxyl from ring B. Position 3 was favored only in the presence of conjugated double bonds between ring A to ring B. This study makes it possible to assign the contribution of different functional groups among the flavonoid subclasses to in vitro inhibition of LDL oxidation.
Vaya
Jacob
J
Laboratory of Natural Medicinal Compounds, Galilee Technological Center, South Industrial Zone, Kiryat Shmona 10200, Israel. vaya@migal.org.il
Mahmood
Saeed
S
Goldblum
Amiram
A
Aviram
Michael
M
Volkova
Nina
N
Shaalan
Amin
A
Musa
Ramadan
R
Tamir
Snait
S
D000578:Amidines / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000145:classification / Q000494:pharmacology; D001713:Biphenyl Compounds; D008078:Cholesterol, LDL / Q000378:metabolism*; D003300:Copper / Q000494:pharmacology; D005419:Flavonoids / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D010851:Picrates / Q000378:metabolism; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D000578:Amidines; D000975:Antioxidants; D001713:Biphenyl Compounds; D008078:Cholesterol, LDL; D005419:Flavonoids; D005609:Free Radicals; D010851:Picrates; C046728:2,2'-azobis(2-amidinopropane); D003300:Copper; C004931:1,1-diphenyl-2-picrylhydrazyl