Tanshinone IIA Interacts with DNA by Minor Groove-Binding(Medicinal Chemistry)
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概要
- 論文の詳細を見る
Tanshen has long been widely used as a traditional Chinese medicine. Tanshinone IIA (Tan IIA) is the most abundant lipophilic constituent of Tanshen which has antitumor activity but the mechanism is poorly understood. Some preliminary reports hypothesized that it is a DNA intercalator and that the furano-o-quinone moiety could produce free radicals responsible for its cytotoxicity. Here the interaction of Tan IIA with DNA was explored in detail using fluorescence, viscosimetry, and molecular modeling. Tan IIA was found to bind with DNA in the minor groove rather than act as an intercalator. Furthermore, the results of immunofluorescence showed that Tan IIA does not produce free radicals in vivo to damage DNA. The former hypothesis was thus negated. The furan oxygen plays the key role in the antitumor ability of Tan IIA because it is involved in the groove-binding, but not in the production of free radicals. The molecular basis illustrated here could be responsible for all the findings in the structure-relationship studies of tanshinone cytotoxicity.
- 公益社団法人日本薬学会の論文
- 2008-12-01
著者
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ZHANG Jing
School of Pharmacy, Second Military Medical University
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GAO Jin
School of Agriculture and Biology, Shanghai Municipality Key Laboratory for Veterinary Biotechnology
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ZHANG Zhichao
State key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai
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Gao Jin
School Of Agriculture And Biology Shanghai Municipality Key Laboratory For Veterinary Biotechnology
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Gao Jin
School Of Environmental And Biological Science And Technology Dalian University Of Technology
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Zhang Zhichao
State Key Lab. Of Fine Chemicals Dalian University Of Technology
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JIN Liji
School of Environmental and Biological Science and Technology, Dalian University of Technology
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SONG Ting
School of Environmental and Biological Science and Technology, Dalian University of Technology
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WU Guiye
State Key Lab. of Fine Chemicals, Dalian University of Technology
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Jin Liji
School Of Environmental And Biological Science And Technology Dalian University Of Technology
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Song Ting
School Of Environmental And Biological Science And Technology Dalian University Of Technology
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Wu Guiye
State Key Lab. Of Fine Chemicals Dalian University Of Technology
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Zhang Jing
School Of Environmental And Biological Science And Technology Dalian University Of Technology
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