title: 9-Nitroanthracene derivative as a precursor of anthraquinone for photodynamic therapy.
abstract: Anthraquinones are typical photosensitizers used in photodynamic therapy (PDT). However, systemic toxicity is a major problem for anthraquinones due to their ability not only to bind DNA but also to cause oxidative stress even without photoirradiation. To avoid such disadvantages in cancer therapy, we designed and synthesized a novel 9-nitroanthracene derivative (1) as a precursor of anthraquinone. Under photoirradiation, 1 is converted into anthraquinone via generation of nitric oxide as confirmed by ESR. Strong DNA cleavage specifically at guanine under photoirradiation was also observed, characteristic of DNA-cleaving reactions by photoirradiated anthraquinones. We propose development of 1 as an alternative approach toward PDT that reduces the systemic toxicity of anthraquinone.
authors.affiliation: Division of Organic Chemistry, National Institute of Health Sciences, Tokyo 158-8501, Japan. fukuhara@nihs.go.jp
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Fukuhara
authors.forename: Shinji
authors.initials: S
authors.lastname: Oikawa
authors.forename: Nana
authors.initials: N
authors.lastname: Hakoda
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sakai
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hiraku
authors.forename: Takuji
authors.initials: T
authors.lastname: Shoda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Saito
authors.forename: Naoki
authors.initials: N
authors.lastname: Miyata
authors.forename: Shosuke
authors.initials: S
authors.lastname: Kawanishi
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Okuda
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000737:chemistry*; D000880:Anthraquinones / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D045744:Cell Line, Tumor; D004247:DNA / Q000187:drug effects; D053837:DNA Cleavage; D004278:DNA, Superhelical / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D010778:Photochemotherapy / Q000379:methods*; D010782:Photolysis; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology / Q000528:radiation effects*; D010957:Plasmids / Q000187:drug effects
chemical_list: D000873:Anthracenes; D000880:Anthraquinones; D004278:DNA, Superhelical; D017319:Photosensitizing Agents; D004247:DNA; C427203:calf thymus DNA; C035016:9-nitroanthracene