A Planar Catechin Analogue as a Promising Antioxidant with Reduced Prooxidant Activity

• Published in: Chemical research in toxicology Vol. 16; no. 1; pp. 81 - 86
• Main Authors: Fukuhara, Kiyoshi, Nakanishi, Ikuo, Shimada, Tomokazu, Ohkubo, Kei, Miyazaki, Kentaro, Hakamata, Wataru, Urano, Shiro, Ozawa, Toshihiko, Okuda, Haruhiro, Miyata, Naoki, Ikota, Nobuo, Fukuzumi, Shunichi
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.01.2003
• Subjects: Antioxidants - chemistry; catechin; Catechin - analogs & derivatives; Catechin - chemistry; Electron Spin Resonance Spectroscopy; Free Radical Scavengers - chemistry; Oxidation-Reduction; Quercetin - chemistry; Structure-Activity Relationship
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx025581f

A planar catechin analogue (1H 2 ), 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 1H 2 produced by the reaction of 1H 2 with 2 equiv of tetramethylammonium methoxide reduced molecular oxygen (O2) to generate superoxide anion (O2 •-). The resulting radical anion (1 • - ) from 1H 2 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 (k et) 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 k et value for 1H 2 implies that, in physiologically relevant systems, there is less of a possibility of generating oxygen radicals responsible for prooxidant activity with 1H 2 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.