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: Kiyoshi Fukuhara, Shinji Oikawa, Nana Hakoda, Yasunori Sakai, Yusuke Hiraku, Takuji Shoda, Shinichi Saito, Naoki Miyata, Shosuke Kawanishi, Haruhiro Okuda
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 15 Issue 11 Pg. 3869-73 (Jun 01 2007) ISSN: 0968-0896 [Print] England
• PMID: 17400461 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracenes
• Anthraquinones
• DNA, Superhelical
• Photosensitizing Agents
• DNA
• calf thymus DNA
• 9-nitroanthracene

Topics

• Animals
• Anthracenes (chemistry)
• Anthraquinones (chemistry, metabolism, toxicity)
• Cell Line, Tumor
• DNA (drug effects)
• DNA Cleavage
• DNA, Superhelical (drug effects)
• Drug Design
• Humans
• Photochemotherapy (methods)
• Photolysis
• Photosensitizing Agents (chemistry, pharmacology, radiation effects)
• Plasmids (drug effects)