Development of next-generation anticancer drugs using dinuclear transition metal complexes
| Project/Area Number |
24590063
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Suzuka University of Medical Science |
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Principal Investigator |
KOMEDA Seiji 鈴鹿医療科学大学, 薬学部, 准教授 (60425056)
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| Co-Investigator(Kenkyū-buntansha) |
UEMURA Masako 鈴鹿医療科学大学, 薬学部, 助手 (70511997)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 制がん剤 / 白金 / DNA / 薬物耐性 / 金属錯体 / テトラゾール / 核酸 / がん / 創薬 / アゾール |
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| Outline of Final Research Achievements |
To construct a structure-activity relationship, twenty-two derivatives of highly in vivo anticancer-active tetrazolato-bridged dinuclear platinum(II) complex were synthesized with variable substituents at tetrazolate C5. Most derivatives were found to be highly in vitro cytotoxic and to circumvent cross-resistance to cisplatin, which is the representative of platinum-based drugs. In addition, the cytotoxicity fingerprints of some derivatives based on the JFCR39 cytotoxicity data were completely different from those of clinical platinum-based anticancer drugs, as well as other anticancer agents. The terazolato-bridged complexes efficiently induce B to C DNA transformation of calf-thymus DNA and compaction of T4 phage DNA. The second- and higher-order structural changes cannot be observed in case of platinum-based drugs. Therefore, tetrazolato-bridged complexes are likely to exhibit cytotoxicity with a novel mechanism of action probably due to the unique interactions with DNA.
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Report
(4 results)
Research Products
(28 results)
