| 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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| 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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