9-Nitroanthracene derivative as a precursor of anthraquinone for photodynamic therapy.
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.
Fukuhara
Kiyoshi
K
Division of Organic Chemistry, National Institute of Health Sciences, Tokyo 158-8501, Japan. fukuhara@nihs.go.jp
Oikawa
Shinji
S
Hakoda
Nana
N
Sakai
Yasunori
Y
Hiraku
Yusuke
Y
Shoda
Takuji
T
Saito
Shinichi
S
Miyata
Naoki
N
Kawanishi
Shosuke
S
Okuda
Haruhiro
H
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
D000873:Anthracenes; D000880:Anthraquinones; D004278:DNA, Superhelical; D017319:Photosensitizing Agents; D004247:DNA; C427203:calf thymus DNA; C035016:9-nitroanthracene