2022 Fiscal Year Final Research Report
Development of the redox controlled Co(III) complexes having hypoxic tumor targeting ligands for solid tumors
| Project/Area Number |
20K05533
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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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| Review Section |
Basic Section 34010:Inorganic/coordination chemistry-related
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| Research Institution | Kansai University |
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Principal Investigator |
Nakai Misaki 関西大学, 化学生命工学部, 准教授 (40527115)
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| Co-Investigator(Kenkyū-buntansha) |
矢野 重信 奈良女子大学, 大和・紀伊半島学研究所, 協力研究員 (60011186)
小倉 俊一郎 東京工業大学, 生命理工学院, 准教授 (90343160)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | Co(III)錯体 / 低酸素腫瘍細胞 / 抗がん薬 |
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| Outline of Final Research Achievements |
It was reported that Co(III) and Co(II) complexes were non-cytotoxic, and that Co(III) complexes have been used as a drug delivery system by coordinating anticancer ligands. However, we found that Co(III) complexes having non-cytotoxic ligands, i.e., polypyridine, exhibited antitumor activities, especially high anti-tumor activities against hypoxic tumor cells. In particular, It was found that Co(III) complex with 4-methyl-1,10-phenanthlorine ligands had the most cytotoxic against hypoxic tumor cells. And, the reduction rate of Co(III) complex with 4-methyl-1,10-phenanthlorine ligands with ascorbic acid is the fastest, suggesting the hypoxia antitumor activities of Co(III) complexes were dependent of their reduction activities. These results suggested that the anticancer activity of Co(III) complexes against hypoxic tumor strongly depends on the reducibility of the Co(III) complexes and their reactivity with ascorbic acid.
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| Free Research Field |
生物無機化学
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| Academic Significance and Societal Importance of the Research Achievements |
低酸素腫瘍細胞は、がんの浸潤や転移といった、がんの悪性化につながるにも関わらず、シスプラチンなどの従来の抗がん薬に対して耐性を持つ。また、溶存酸素を利用する光線力学的療法や、放射線治療も効果が期待できず、低酸素腫瘍細胞に効果的な抗がん薬の開発がの望まれている。Co(III)錯体自体が、従来抗がん作用はないと報告されてきた。しかしながら、Co(III)錯体自体の抗がん作用と抗がん作用メカニズムが解明されれば、低酸素腫瘍細胞の治療に加えて、今まで抗がん薬として開発されてきたPt錯体、Pd錯体、Ru錯体のような、高価な金属に代わって、安価な抗がん薬の開発につながる。
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