論文

査読有り
2015年6月

Synthesis and biological activities of the amide derivative of aplog-1, a simplified analog of aplysiatoxin with anti-proliferative and cytotoxic activities

Biosci. Biotechnol. Biochem.
  • Yusuke Hanaki
  • ,
  • Ryo C. Yanagita
  • ,
  • Takahiro Sugahara
  • ,
  • Misako Aida
  • ,
  • Harukuni Tokuda
  • ,
  • Nobutaka Suzuki
  • ,
  • Kazuhiro Irie

79
6
開始ページ
888
終了ページ
895
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1080/09168451.2014.1002452
出版者・発行元
TAYLOR & FRANCIS LTD

Aplog-1 is a simplified analog of the tumor-promoting aplysiatoxin with anti-proliferative and cytotoxic activities against several cancer cell lines. Our recent findings have suggested that protein kinase C delta (PKC delta) could be one of the target proteins of aplog-1. In this study, we synthesized amide-aplog-1 (3), in which the C-1 ester group was replaced with an amide group, to improve chemical stability in vivo. Unfortunately, 3 exhibited seventy-fold weaker binding affinity to the C1B domain of PKC delta than that of aplog-1, and negligible anti-proliferative and cytotoxic activities even at 10(-4)M. A conformational analysis and density functional theory calculations indicated that the stable conformation of 3 differed from that of aplog-1. Since 27-methyl and 27-methoxy derivatives (1, 2) without the ability to bind to PKC isozymes exhibited marked anti-proliferative and cytotoxic activities at 10(-4)M, 3 may be an inactive control to identify the target proteins of aplogs.

リンク情報
DOI
https://doi.org/10.1080/09168451.2014.1002452
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000356239400004&DestApp=WOS_CPL
共同研究・競争的資金等の研究課題
抗がん剤開発を指向した新規PKCリガンドの創製と作用機構解析
ID情報
  • DOI : 10.1080/09168451.2014.1002452
  • ISSN : 0916-8451
  • eISSN : 1347-6947
  • Web of Science ID : WOS:000356239400004

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