Multiple Recognition of DNA by dinuclear platinum complexes with effective cell growth inhibition in cisplatin resistant cell lines
| Project/Area Number |
20590045
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Osaka University of Pharmaceutical Sciences |
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Principal Investigator |
CHIKUMA Masahiko Osaka University of Pharmaceutical Sciences, 薬学部, 学長 (50025699)
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| Co-Investigator(Kenkyū-buntansha) |
SATO Takaji 大阪薬科大学, 薬学部, 講師 (80257899)
SAITO Yoshihiro 大阪薬科大学, 薬学部, 講師 (90186974)
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| Co-Investigator(Renkei-kenkyūsha) |
KOMEDA Seiji 鈴鹿医療科学大学, 薬学部, 助教 (60425056)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2008: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 核酸 / 抗がん剤 / 物理系薬学 / 分子認識 / 複核白金錯体 / 白金錯体 / シスプラチン / 複核錯体 / 非共有結合性相互作用 |
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| Research Abstract |
Both mechanisms of anti-tumor activity and cellular resistance to platinum complexes are believed to be related with coordination binding mode of platinum complexes with DNA. Polynuclear complexes are expected to interact variously with DNA and to have different mechanism of action from that of mononuclear complexes such as cisplatin, one of the most effective anti-tumor agents. In an attempt to search for more active platinum complexes and to overcome cisplatin resistance, we have developed a dinuclear platinum(II) cation complex, [{cis-Pt(NH_3)_2}_2(μ-pyrazolato) (μ-OH)](NO_3)_2 (AMPZ) and its derivatives using pyrazole analogues as bridging ligands. These platinum complexes were effective to cisplatin-resistant tumor cell lines. AMPZ was found to interact covalently and non-covalently with DNA. In this study we focused to non-covalent binding mode of AMPZ with DNA and investigated with various methods.The non-covalent binding mode of AMPZ with DNA has been found to an electrostatic interaction. It remains to be elucidated whether the anti-tumor activity of AMPZ is attributed to the non-covalent binding of AMPZ with DNA or not.
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Report
(4 results)
Research Products
(41 results)
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[Journal Article] Novel and simple loading of cisplatin into liposomes and targeting tumor endothelial cells2010
Author(s)
Hirai M., Minematsu H., Hiramatsu Y., Kitagawa H., Otani T., Iwashita S., Kudoh T., Chen L., Li Y., Okada M., Salomon D .S. , Igarashi K., Chikuma M., Seno M.
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Journal Title
International Journal Pharmaceutics 391
Pages: 274-283
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