2012 Fiscal Year Final Research Report
Development of a palmitic acid-derived anticancer drug for the treatment of human colon cancer
| Project/Area Number |
22501050
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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 |
Clinical oncology
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| Research Institution | Nagoya City University |
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Principal Investigator |
SUZUI Masumi 名古屋市立大学, 大学院・医学研究科, 教授 (30347158)
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| Co-Investigator(Renkei-kenkyūsha) |
IINUMA Munekazu 岐阜薬科大学, 薬学部, 教授 (70082998)
YOSHIDA Ichiro 岐阜薬科大学, 薬学部, 助教 (40432447)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 脂肪酸誘導体 / 抗がん剤 / 大腸がん / 構造活性相関 / リード化合物 |
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| Research Abstract |
The final goal of the present study was to develop a fatty acid-derived anticancer drug for the treatment of human colon cancer. We decided to use the natural fatty acid decenoic acid and palmitic acid as lead compounds. Using quantitative structure activity relationship (QSAR) analysis, we found that a saturated aliphatic tail of 16 carbon atoms and a side chain at the C-1 position composed of piperidine rings markedly contribute to the in vitro anticancer effects of the palmitic acid derivatives. Compound code 903 was determined to be the most effective anticancer agent, which was less toxic to normal epithelial cells. In a nude mouse xenograft model, this agent inhibited the growth of implanted tumor cells. We estimated that the effective dose of ip treatment would be 0.025-0.05 mg/kg. Compound code 903 was thought to be absorbed from gastrointestinal tract by values of pKa and cLogD. The drug code 903 may be a promising lead compound for the treatment of colon cancer and other solid tumors because of its broad cancer killing activity and significant tumor specificity.
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