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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.

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  • Publisher Full Text
  • Authors

    Kumar S, Gautam S, Sharma A

    Source

    Mutation research 755:1 2013 Jul 4 pg 30-41

    MeSH

    Anticoagulants
    Antifibrinolytic Agents
    Antimutagenic Agents
    Antineoplastic Agents
    Antioxidants
    Drug Resistance, Bacterial
    Escherichia coli
    Molecular Structure
    Naphthoquinones
    Nucleic Acid Synthesis Inhibitors
    Oxidation-Reduction
    Oxidative Stress
    Reactive Oxygen Species
    Rifampin
    Salmonella typhimurium
    Structure-Activity Relationship
    Vitamin K 3

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    23688616