期刊
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
卷 86, 期 8, 页码 1013-1023出版社
OXFORD UNIV PRESS
DOI: 10.1093/bbb/zbac084
关键词
protein kinase C; aplysiatoxin; simplified analog; antiproliferative activity; cyclic ketal
类别
资金
- Japan Society for the Promotion of Science (JSPS) KAKENHI [17H06405]
A simplified analog of aplysiatoxin (ATX) was synthesized with fewer steps and exhibited comparable antiproliferative activity to the reference compound. Carvone may be a potential candidate for a more synthetically accessible drug.
Simplified analogs of aplysiatoxin (ATX) such as 10-Me-aplog-1 exhibit potent antiproliferative activity toward human cancer cell lines by activating protein kinase C (PKC). However, the synthesis of 10-Me-aplog-1 involved a 23-step longest linear sequence (LLS). Therefore, we have been working toward the development of a more synthetically accessible analog of ATX. In this study, we designed a new analog of ATX wherein a cyclic ketal moiety derived from (R)-(-)-carvone replaced the spiroketal moiety in 18-deoxy-aplog-1. The new analog's synthesis proceeded in an 8-step LLS. Although the configuration at position 3 of the cyclic ketal in the (R)-(-)-carvone-based analog was opposite to those of ATX and 18-deoxy-aplog-1, the antiproliferative activity toward human cancer cell lines of the carvone-based analog was comparable with that of 18-deoxy-aplog-1. The obtained results indicate the potential of the carvone-based analog as a basis for discovering PKC-targeting molecules requiring a decreased number of synthetic steps.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据