title: Preparation and antioxidant/pro-oxidant activities of 3-monosubstituted 5-hydroxyoxindole derivatives.
abstract: Antioxidant treatments have been expected to be a novel therapeutics for various oxidative stress-mediated disorders. Our previous study revealed that 5-hydroxyoxindole and its 3-phenacyl-3-hydroxy derivatives showed excellent antioxidant activities such as 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and lipid-peroxidation inhibitory activity. However, the DPPH radical scavenging activity of the 3,3-disubstituted derivatives was lower than that of the original 5-hydroxyoxindole. In the present study, we synthesized novel 3-monosubstituted 5-hydroxyoxindole derivatives that exhibited stronger DPPH radical scavenging activities and lipid peroxidation-inhibitory activities than the 3,3-disubstituted 5-hydroxyoxindoles. Moreover, the 3-monosubstituted 5-hydroxyoxindole derivatives showed neither an iron-mediated pro-oxidant effect nor a remarkable cytotoxicity against HL-60 cell lines except some of the highly lipophilic compounds. These results indicate that 3-monosubstituted 5-hydroxyoxindoles can be used as a promising antioxidant scaffold for drug discovery.
authors.affiliation: Department of Pharmaceutical Sciences, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yasuda
authors.affiliation: Department of Pharmaceutical Sciences, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Pharmaceutical Sciences, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohe
authors.affiliation: Department of Chemistry, Nippon Medical School, 1-7-1 Kyonan-cho, Musashino-shi, Tokyo 180-0023, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Pharmaceutical Sciences, Keio University Faculty of Pharmacy, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Mashino
keywords: 5-hydroxyoxindole; antioxidant; lipid peroxidation; pro-oxidant effect; radical scavenging activity