title: Effects of quinone derivatives, such as 1,4-naphthoquinone, on DNA polymerase inhibition and anti-inflammatory action.
abstract: Previously, we reported that vitamin K(3), which consists of a quinone component, inhibits the activity of human DNA polymerase γ (pol γ). In this study, we investigated the inhibitory effects of 4 quinone derivatives (1,4-benzoquinone (BQ), 1,4-naphthoquinone (NQ), 9,10-anthraquinone (AQ) and 5,12-naphthacenequinone (NCQ)) on the activity of mammalian pols. BQ and NQ potently inhibited the activity of all the pol species: pols α, β, γ, δ, ε and λ, and NQ was a stronger pol inhibitor than BQ. Because we previously found a positive relationship between pol l inhibition and anti-inflammatory action, we examined whether these quinone derivatives could inhibit inflammatory responses. BQ and NQ caused a marked reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute inflammation in mouse ear, although AQ and NCQ did not. In a cell culture system using mouse macrophages, NQ displayed the strongest suppression in the production of tumor necrosis factor (TNF)-α induced by lipopolysaccharide (LPS) among the quinone derivatives tested. Moreover, NQ was found to inhibit the action of nuclear factor (NF)-κ. In an in vivo mouse model of LPS-evoked acute inflammation, intraperitoneal injection of BQ and NQ to mice led to suppression of TNF-α production in serum. These anti-inflammatory responses of NQ were more potent than those of BQ. In conclusion, this study has identified several quinone derivatives, such as NQ, that are promising anti-inflammatory candidates.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nishida
authors.forename: Midori
authors.initials: M
authors.lastname: Hirai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mizushina
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D015751:Genes, pol; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009285:Naphthoquinones / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors; D051381:Rats; D024483:Vitamin K 3 / Q000494:pharmacology*
chemical_list: D000880:Anthraquinones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000933:Antifibrinolytic Agents; D004791:Enzyme Inhibitors; D009285:Naphthoquinones; D019384:Nucleic Acid Synthesis Inhibitors; D024483:Vitamin K 3; D004259:DNA-Directed DNA Polymerase; C035342:1,4-naphthoquinone