Furanoterpenes, new types of protein tyrosine phosphatase 1B inhibitors, from two Indonesian marine sponges, Ircinia and Spongia spp

[Display omitted] Protein tyrosine phosphatase (PTP) 1B negatively regulates the insulin and leptin signaling pathways, and, thus, the clinical application of PTP1B inhibitors to the prevention and treatment of type 2 diabetes and obesity is expected. During our studies on PTP1B inhibitors, two fura...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2017-03, Vol.27 (5), p.1159-1161
Main Authors: Abdjul, Delfly B., Yamazaki, Hiroyuki, Kanno, Syu-ichi, Wewengkang, Defny S., Rotinsulu, Henki, Sumilat, Deiske A., Ukai, Kazuyo, Kapojos, Magie M., Namikoshi, Michio
Format: Article
Language:English
Subjects:
Animals
C21 furanoterpene
Cell Line, Tumor
Drug Screening Assays, Antitumor
Enzyme Inhibitors - pharmacology
Furanosesterterpene
Furans - pharmacology
Humans
Inhibitor
Marine sponge
Mice, Knockout
Porifera - chemistry
Protein tyrosine phosphatase 1B
Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors
Protein Tyrosine Phosphatase, Non-Receptor Type 1 - genetics
Proteins - pharmacology
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Summary:[Display omitted] Protein tyrosine phosphatase (PTP) 1B negatively regulates the insulin and leptin signaling pathways, and, thus, the clinical application of PTP1B inhibitors to the prevention and treatment of type 2 diabetes and obesity is expected. During our studies on PTP1B inhibitors, two furanosesterterpenes and a C21 furanoterpene were obtained as new types of PTP1B inhibitors from two Indonesian marine sponges. (7E, 12E, 20Z, 18S)-Variabilin (1) and (12E, 20Z, 18S)-8-hydroxyvariabilin (2) from Ircinia sp. and furospongin-1 (3) from Spongia sp. inhibited PTP1B activity with IC50 values of 1.5, 7.1, and 9.9μM, respectively. The inhibitory activity of compound 1 against T-cell PTP (TCPTP) was approximately 2-fold that against PTP1B, whereas the vaccinia H-1-related phosphatase (VHR) inhibitory effects of 1 were 4-fold weaker than that of its PTP1B inhibitory activity. Compounds 1–3 at 50μM did not show cytotoxicity against two human cancer cell lines, hepatoma Huh-7 and bladder carcinoma EJ-1. Compound 1 did not enhance the phosphorylation level of Akt, a key downstream effector of the cascade, in Huh-7 cells.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2017.01.071