title: Antimutagenic and antioxidant properties of plumbagin and other naphthoquinones.
abstract: The structure-function relationships of the naphthoquinone phytochemicals, plumbagin, juglone, and menadione, have been studied with regard to antimutagenic and antioxidant activities. Antimutagenicity of these compounds was assessed by the Ames test and RNA polymerase B (rpoB)-based rifampicin resistance assay. Antioxidant potential was evaluated by radical scavenging assays and reducing power measurement. Protection of cells and DNA against gamma radiation-induced oxidative damage was assayed by survival analysis and gel electrophoresis profiling, respectively. On the 1,4-naphthoquinone nucleus, plumbagin possesses 5-hydroxyl and 2-methyl functional groups, whereas juglone has only the 5-hydroxyl and menadione only the 2-methyl group. Plumbagin showed strong antimutagenic (against ultraviolet and ethyl methanesulfonate) and antioxidant activities, whereas juglone displayed only strong antimutagenic, and menadione only strong antioxidant activities. Thus, these two functional groups (5-OH/2-CH3) play important roles in the differential bioactivity of naphthoquinones. Escherichia coli, microarray analysis showed upregulation of the genes rep (replication/repair), ybaK (tRNA editing), speE (spermidine synthesis), and yjfC (glutathionyl spermidine synthesis) by plumbagin or juglone, and sodC (superoxide dismutase), xthA (oxidative repair), hycB (electron carrier between hydrogenase 3 and fumarate dehydrogenase), and ligA (formation of phosphodiester bond in DNA) by plumbagin or menadione. Studies with E. coli single-gene knockouts showed that ybaK and speE, reported to prevent mistranslation, are likely to be involved in the antimutagenicity displayed by juglone, and sodC to be involved in the antioxidant activity of menadione.
authors.affiliation: Food Technology Division, Bhabha Atomic Research Centre, Mumbai, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: Satyendra
authors.initials: S
authors.lastname: Gautam
authors.forename: Arun
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D016587:Antimutagenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects*; D015394:Molecular Structure; D009285:Naphthoquinones / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects*; D013329:Structure-Activity Relationship; D024483:Vitamin K 3 / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D016587:Antimutagenic Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D009285:Naphthoquinones; D019384:Nucleic Acid Synthesis Inhibitors; D017382:Reactive Oxygen Species; D024483:Vitamin K 3; D012293:Rifampin; C005134:juglone; C014758:plumbagin
keywords: AP; Antimutagenicity; Antioxidant; JU; Knockouts; ME; Microarray; Naphthoquinones; PL; Rif(R); SPC; SR; WT; aRNA; amplified RNA; antimutagenic potential; cfu; colony-forming units; his; histidine; juglone; menadione; plumbagin; rifampicin resistant; spontaneous reversion; standard plate count; wild type.