Development of new therapeutic agents derived from Wnt signaling inhibitor for treating brain cancer
Description: 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.
Amount: ¥3,770,000
Funding type: research
Funder scheme: Grant-in-Aid for Challenging Exploratory Research
Start date: 2015-04-01
End date: 2018-03-31
Investigator: Takehiko Yoshimitsu
Institution: Okayama University(2016-2017)Osaka University(2015)
Funded outputs count: 6
Funder award ID: 15K14977
OpenAlex ID: G8590802496