Antioxidant activities of 5-hydroxyoxindole and its 3-hydroxy-3-phenacyl derivatives: the suppression of lipid peroxidation and intracellular oxidative stress.
The antioxidant activities of 5-hydroxyoxindole (1) and newly synthesized 3,5-dihydroxy-3-phenacyl-2-oxindole derivatives against rat liver microsome/tert-butylhydroperoxide system-induced lipid peroxidation and hydrogen peroxide-induced intracellular oxidative stress were investigated. Compound 1 and its derivatives showed significant suppression of lipid peroxidation and an intracellular oxidative stress. The effects of the more lipophilic derivatives tended to be greater than that of the original compound 1. The cytotoxicity of all of the oxindole derivatives on human promyelocytic leukemia HL60 cells was lower than that of 2,6-di(tert-butyl)-4-hydroxytoluene (BHT), a widely used phenolic antioxidant. These results show that compound 1 and its 3-substituted derivatives could be good lead candidates for future novel antioxidant therapeutics.
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo, Japan.
Daisuke
D
Yasuda
Kyoko
K
Takahashi
Tomoyuki
T
Ohe
Shigeo
S
Nakamura
Tadahiko
T
Mashino
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects*; D000078183:Oxindoles; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D020122:tert-Butylhydroperoxide / Q000037:antagonists & inhibitors / Q000494:pharmacology
C484744:5-hydroxyoxindole; D000970:Antineoplastic Agents; D000975:Antioxidants; D007211:Indoles; D000078183:Oxindoles; C019188:3-hydroxy-3-phenacyloxindole; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide
5-Hydroxyoxindole; Antioxidant; Lipophilicity; Oxidative stress; Radical scavenging activity