Effects of structural modification on the DNA binding properties and photo-induced cleavage reactivity of propargylic sulfones conjugated with an anthraquinone structure.
Propargylic sulfones are known as pH-dependent DNA cleaving agents. We have designed a novel propargylic sulfone conjugated with an anthraquinone structure and evaluated its DNA binding and cleavage characteristics. The propargylic sulfone 3 showed high intercalating ability attributable to anthraquinone chromophore, leading to the efficient alkylation of DNA. The anthraquinone chromophore in 3 also acted as a photosensitizer, and photoirradiation of 3 with DNA induced one-electron oxidation, resulting in the further DNA cleavage. Evaluation of the effect of 3 against EMT6/KU cells revealed that 3 exhibited potent cytotoxicity, even without photoirradiation.
Haruna
Ken-ichi
K
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Kyoto University Katsura, Nishikyo-ku, Japan.
Kanezaki
Hiroshi
H
Tanabe
Kazuhito
K
Dai
Wei-Min
WM
Nishimoto
Sei-ichi
S
D000480:Alkynes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000880:Anthraquinones / Q000737:chemistry*; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000528:radiation effects; D007510:Isatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008027:Light; D051379:Mice; D010782:Photolysis; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000480:Alkynes; D000880:Anthraquinones; D018906:Antineoplastic Agents, Alkylating; D017319:Photosensitizing Agents; C116442:propargylic sulfone; D007510:Isatin; D004247:DNA