2017 Fiscal Year Final Research Report
Development of new therapeutic agents derived from Wnt signaling inhibitor for treating brain cancer
| Project/Area Number |
15K14977
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
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| Research Institution | Okayama University (2016-2017)
Osaka University (2015) |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | アルカロイド / 脳腫瘍 / agelastatin A / Wnt/β-cateninシグナル阻害 / 抗がん剤 / 創薬 |
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| Outline of Final Research Achievements |
Agelastatin A (AA) exhibits potent antiproliferative activity against cancer cell lines by inhibiting the Wnt/beta-catenin pathway responsible for cellular processes. The present study was undertaken to develop new therapeutic agents derived from AA for treating brain cancer and has culminated in the following achievements. 1) A new synthetic route to AA and AA derivatives was established by employing radical azidation of a silyl enol ether. The route enabled facile access to AA analogs with varying N1-substituents. Furthermore, AA analogs that exhibit potent inhibitory activity were identified by the structure-activity relationship (SAR) study. 2) A new method for the catalytic radical oxyazidation of alkenes was developed. 3) The divergent synthetic route successfully provided access to three chemical probes applicable for identifying the molecular target of AA. However, none of the probes were found to exert desirable activities.
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| Free Research Field |
有機合成化学、創薬化学
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