The Interactions of (-)-(R)-2-Aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)platinum(II)Monohydrate (DWA2114R) and Related Compounds with Deoxyribonucleic Acid

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概要

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• The interactions of a new antitumor platinum (Pt) complex, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)platinum(II) monohydrate (DWA2114R, 2) and its related compounds, cis-diamminedichloroplatinum(II)(CDDP, 2), trans-diamminedichloroplatium(II)(TDDP, 3), (+)-(S)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)platinum(II) monohydrate (DWA2114S, 4), (R)-2-aminomethylpyrrolidinedichloroplatinum(II)(5) and cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II)(CBDCA, 6), with calf-thymus deoxyribonucleic acid (DNA)and DNA nucleosides were investigated by ultraviolet (UV) and circular dichroism (CD) spectrometry.The UV spectra of the DNAs treated with these Pt complexes exhibited both bathochromic shift and hyperchromicity, showing a binding of Pt to the heterocyclic groups of these DNA as well as an alteration in the secondary structure of DNA. The reaction rates of the Pt complexes with DNA, however, differed from one another, and the order was CDDP, TDDP, 5≫DWA2114R, S>CBDCA.The CD spectra of the DNAs treated with the Pt complexes, except TDDP, at a low Pt ratio (<approximately(ca.)0.1 of Pt bound to DNA/DNA base molar ratio) exhibited an increase of ellipticity at ca. 275nm.The melting temperature of the DNAs treated with DWA2114R of CDDP were almost the same as the native DNA, while the melting temperature with TDDP was higher by 7-8℃ than that of the native DNA.All the Pt complexes reacted with 2'-deoxyguanosine (dG), 2'-deoxyadenosine and 2'-deoxycytidine, but none reacted with thymidene. The CD spectral change of the dG was largest. DWA2114R reacted faster with dG than other mucleosides.

• 社団法人日本薬学会の論文
• 1992-01-25

著者

• 松本 智子

  Exploratory Research Laboratories Chugai Pharmaceutical Co. Ltd.

• 森川 一実

  Exploratory Research Laboratories, Chugai Pharmaceutical Co., Ltd.,

• 松岡 幸雄

  Exploratory Research Laboratories, Chugai Pharmaceutical Co., Ltd.,

• 小泉 [キン]也

  Exploratory Research Laboratories, Chugai Pharmaceutical Co., Ltd.,

• 松岡 幸雄

  Exploratory Research Laboratories Chugai Pharmaceutical Co. Ltd.

• 森川 一実

  Exploratory Research Laboratories Chugai Pharmaceutical Co. Ltd.

• 小泉 也

  Exploratory Research Laboratories Chugai Pharmaceutical Co. Ltd.

関連論文

• The Interactions of (-)-(R)-2-Aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)platinum(II)Monohydrate (DWA2114R) and Related Compounds with Deoxyribonucleic Acid
• Synthesis of Platinum Complexes of 2-Aminomethylpyrrolidine Derivatives for Use as Carrier Ligands and Their Antitumor Activities
• 2-Aminoalkylpyridineをキャリヤーリガンドとする白金錯体のColon26結腸癌に対する制癌活性及び血漿蛋白質との反応性について
• 2-Aminoalkylpyridine をキャリヤーリガンドとする白金錯体の合成とその制癌活性について

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