title: Inhibition of LDL oxidation by flavonoids in relation to their structure and calculated enthalpy.
abstract: 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.
authors.affiliation: Laboratory of Natural Medicinal Compounds, Galilee Technological Center, South Industrial Zone, Kiryat Shmona 10200, Israel. vaya@migal.org.il
authors.forename: Jacob
authors.initials: J
authors.lastname: Vaya
authors.forename: Saeed
authors.initials: S
authors.lastname: Mahmood
authors.forename: Amiram
authors.initials: A
authors.lastname: Goldblum
authors.forename: Michael
authors.initials: M
authors.lastname: Aviram
authors.forename: Nina
authors.initials: N
authors.lastname: Volkova
authors.forename: Amin
authors.initials: A
authors.lastname: Shaalan
authors.forename: Ramadan
authors.initials: R
authors.lastname: Musa
authors.forename: Snait
authors.initials: S
authors.lastname: Tamir
mesh_terms: 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
chemical_list: 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