title: A planar catechin analogue as a promising antioxidant with reduced prooxidant activity.
abstract: A planar catechin analogue (1H2), in which catechol and chroman moieties in (+)-catechin are constrained to be coplanar, is an efficient radical scavenger compared to the native catechin, and are nearly as effective as quercetin, a strong radical scavenger. The dianion (1(2-)) of 1H2 produced by the reaction of 1H2 with 2 equiv of tetramethylammonium methoxide reduced molecular oxygen (O2) to generate superoxide anion (O2*-). The resulting radical anion (1*-) from 1H2 underwent intramolecular proton transfer to give an o-semiquinone radical anion form of 1*-, which shows a characteristic ESR spectrum with g value of 2.0048. Although the same mechanism has also been shown for (+)-catechin, the rate constant of electron transfer (ket) from 1(2-) to O2 is about a half of that reported for (+)-catechin, indicating that the electron transfer from 1(2-) to O2 is slower than that from (+)-catechin dianion to O2. Together with efficient protection against DNA strand breakage induced by the Fenton reaction, the small ket value for 1H2 implies that, in physiologically relevant systems, there is less of a possibility of generating oxygen radicals responsible for prooxidant activity with 1H2 than that with (+)-catechin. The strong radical scavenging ability and less-efficient generation of O2*- suggest that the planar catechin analogue may be useful for the prevention and/or treatment of free-radical-associated diseases.
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan. fukuhara@nihs.go.jp
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fukuhara
authors.forename: Ikuo
authors.initials: I
authors.lastname: Nakanishi
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Shimada
authors.forename: Kei
authors.initials: K
authors.lastname: Ohkubo
authors.forename: Kentaro
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Wataru
authors.initials: W
authors.lastname: Hakamata
authors.forename: Shiro
authors.initials: S
authors.lastname: Urano
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ozawa
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Okuda
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyata
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ikota
authors.forename: Shunichi
authors.initials: S
authors.lastname: Fukuzumi
mesh_terms: D000975:Antioxidants / Q000737:chemistry*; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000737:chemistry*; D010084:Oxidation-Reduction; D011794:Quercetin / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D002392:Catechin; D011794:Quercetin