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Title: Synthesis and biological activities of the amide derivative of aplog-1, a simplified analog of aplysiatoxin with anti-proliferative and cytotoxic activities.
Authors: Hanaki, Yusuke
Yanagita, Ryo C
Sugahara, Takahiro
Aida, Misako
Tokuda, Harukuni
Suzuki, Nobutaka
Irie, Kazuhiro  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: 入江, 一浩
Keywords: aplysiatoxin
protein kinase C
tumor promoter
Issue Date: 2015
Publisher: Taylor & Francis Group
Journal title: Bioscience, biotechnology, and biochemistry
Volume: 79
Issue: 6
Start page: 888
End page: 895
Abstract: 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 Cδ (PKCδ) 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 PKCδ 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.
Description: Published online: 23 Jan 2015
Rights: This is an Accepted Manuscript of an article published by Taylor & Francis in 'Bioscience, biotechnology, and biochemistry' available online:
The full-text file will be made open to the public on 23 Jan 2016 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1080/09168451.2014.1002452
PubMed ID: 25612633
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