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.
- ,
- ,
- ,
- ,
- ,
- ,
- 巻
- 79
- 号
- 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
- ID情報
-
- DOI : 10.1080/09168451.2014.1002452
- ISSN : 0916-8451
- eISSN : 1347-6947
- Web of Science ID : WOS:000356239400004