Abstract |
Three unique sesquiterpenes, named euryspongins A-C (1-3), have been isolated from the marine sponge Euryspongia sp. The absolute configuration of 1 was assigned as (4R,6R,9S) by comparing its experimental Electronic Circular Dichroism (ECD) spectrum with the calculated ECD spectra of both enantiomers, and the absolute configurations of 2, 3 and artifact 4 were suggested on the basis of that of 1 by assuming common biogenesis of 1-3. These absolute configurations were opposite to those depicted in the previous communication. Further separation of the remaining fractions lead to the isolation of a new C11-polyketide, named as eurydiene (5), together with a known C11-polyketide, nakitriol (6). The structure of 5 was assigned on the basis of its spectroscopic data as a bicyclic alcohol with a diene side chain. Dehydroeuryspongin A (4) inhibited protein tyrosine phosphatase 1B (PTP1B), an important target enzyme for the treatment of type II diabetes and obesity, with an IC50 value of 3.58μM. Moreover, compound 4 did not inhibit the proliferation of human hepatoma Huh-7 cells at 100μM. One of the locations in which PTP1B has been detected is hepatocytes. Compounds 1-3, 5, and 6 were not active against PTP1B. The growth of human colon (HCT-15) and T-cell lymphoma (Jurkat) cells was not disturbed by compounds 1-6.
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Authors | Hiroyuki Yamazaki, Ohgi Takahashi, Syu-Ichi Kanno, Takahiro Nakazawa, Shiori Takahashi, Kazuyo Ukai, Deiske A Sumilat, Masaaki Ishikawa, Michio Namikoshi |
Journal | Bioorganic & medicinal chemistry
(Bioorg Med Chem)
Vol. 23
Issue 4
Pg. 797-802
(Feb 15 2015)
ISSN: 1464-3391 [Electronic] England |
PMID | 25600405
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Ltd. All rights reserved. |
Chemical References |
- Biological Products
- Sesquiterpenes
- Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Topics |
- Animals
- Biological Products
(chemistry, isolation & purification, pharmacology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Diabetes Mellitus, Type 2
(drug therapy, enzymology)
- Humans
- Models, Molecular
- Neoplasms
(drug therapy)
- Porifera
(chemistry)
- Protein Tyrosine Phosphatase, Non-Receptor Type 1
(antagonists & inhibitors, metabolism)
- Sesquiterpenes
(chemistry, isolation & purification, pharmacology)
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