Spectroscopic Investigation on the Interaction of NCA0424,a Potent Antitumor Indoloquinoxaline Derivative, with DNA
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概要
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NCA0424 (1), an indoloquinoxaline derivative, has a potent antitumor activity against in vitro and in vivo tumor models. To elucidate its structure-activity relationship, the interactions with various B-form DNAs were investigated by thermal denaturation, viscosity and circular dichroism (CD) measurements. The thermal stability of the DNA duplex was increased by the interaction with 1,and preferable binding for alternative purine-pyrimidine base sequence was suggested. Comparative viscometric measurements with ethidium bromide (an intercalator) and distamycin (a minor groove binder) suggested that 1 is an intercalator. The interaction of DNA with 1 revealed a new CD band at 340-390 nm. Taking advantage of this induced CD band, the equilibrium binding constants were determined for various DNAs, and the binding preference of 1 for the alternative purine-pyrimidine base sequence, especially for the case of guanine as purine base, was indicated. The appearance of the induced CD band implies the importance of 1 side chain for the effective and/or stable intercalation of the aromatic ring into the DNA base pair.
- 社団法人日本薬学会の論文
- 1998-05-15
著者
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北村 和則
富山化学工業株式会社綜合研究所
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DOI Mitsunobu
Osaka University of Pharmaceutical Sciences
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Doi Mitsunobu
Department Of Physical Chemistry Osaka University Of Pharmaceutical Sciences
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Doi Mitsunobu
Department Of Pyysical Chemistry Osaka University Of Pharmaceutical Sciences
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ISHIDA Toshimasa
Department of Pyysical Chemistry, Osaka University of Pharmaceutical Sciences
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KITAMURA Kunihiro
Research Center of Taisho Pharmaceutical Co., Ltd.
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TARUI Mariko
Osaka University of Pharmaceutical Sciences
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MIHARA Yoshitetsu
Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences
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HAMA Yumiko
Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences
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HANATANI Akemi
Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences
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TARUI Mariko
Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences
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NAKAIKE Shiro
Research Center of Taisho Pharmaceutical Co., Ltd.,
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Ishida T
Osaka Univ. Pharmaceutical Sci. Osaka
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Ishida Toshimasa
Department Of Physical Chemistry Osaka University Of Pharmaceutical Sciences
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Kitamura Keisuke
Kyoto Pharmaceutical University
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Hama Y
Department Of Physical Chemistry Osaka University Of Pharmaceutical Sciences
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Nakaike S
Taisho Pharmaceutical Co. Ltd. Saitama Jpn
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Hanatani Akemi
Department Of Physical Chemistry Osaka University Of Pharmaceutical Sciences
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Ishida T
Departments Of Biochemistry Shiga University Of Medical Science
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Kitamura K
Kyoto Pharmaceutical University
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北村 和則
Kyoto Pharmaceutical University
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Hama Yumiko
Department Of Physical Chemistry Osaka University Of Pharmaceutical Sciences
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Ishida Toshimasa
Osaka Univ. Of Pharmaceutical Sciences
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Mihara Yoshitetsu
Department Of Physical Chemistry Osaka University Of Pharmaceutical Sciences
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Nakaike Shiro
Research Center of Taisho Pharmaceutical Co., Ltd.
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