A bromopyrrole-containing diterpene alkaloid from the Okinawan marine sponge Agelas nakamurai activates the insulin pathway in Huh-7 human hepatoma cells by inhibiting protein tyrosine phosphatase 1B

Hiroyuki Yamazaki; Syu-Ichi Kanno; Delfly B Abdjul; Michio Namikoshi

doi:10.1016/j.bmcl.2017.03.033

A bromopyrrole-containing diterpene alkaloid from the Okinawan marine sponge Agelas nakamurai activates the insulin pathway in Huh-7 human hepatoma cells by inhibiting protein tyrosine phosphatase 1B

Bioorg Med Chem Lett. 2017 May 15;27(10):2207-2209. doi: 10.1016/j.bmcl.2017.03.033. Epub 2017 Mar 18.

Authors

Hiroyuki Yamazaki¹, Syu-Ichi Kanno², Delfly B Abdjul³, Michio Namikoshi⁴

Affiliations

¹ Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan. Electronic address: yamazaki@tohoku-mpu.ac.jp.
² Department of Clinical Pharmacotherapeutics, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan. Electronic address: syu-kan@tohoku-mpu.ac.jp.
³ Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan; Faculty of Fisheries and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia.
⁴ Department of Natural Product Chemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan.

PMID: 28389151
DOI: 10.1016/j.bmcl.2017.03.033

Abstract

Agelasine G (1), a known bromine-containing diterpene alkaloid, was isolated as a new type of protein tyrosine phosphatase (PTP) 1B inhibitor together with ageline B (2), an inactive debromo-derivative of 1, from the marine sponge Agelas nakamurai collected at Iriomote Island in Okinawa, Japan. Further biological evaluations revealed that compound 1 exhibited selective inhibitory activity against PTP1B over T-cell PTP and CD45 phosphatase. Compound 1 also enhanced the insulin-stimulated phosphorylation levels of Akt in Huh-7 cells more strongly than compound 2. The results obtained in this study suggest that compound 1 activates the insulin signaling pathway by inhibiting PTP1B activity.

Keywords: Agelasine G; Ageline B; Inhibitor; Marine sponge; Protein tyrosine phosphatase 1B.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Agelas / chemistry*
Agelas / metabolism
Alkaloids / chemistry*
Alkaloids / isolation & purification
Alkaloids / toxicity
Animals
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
Diterpenes / chemistry*
Diterpenes / isolation & purification
Diterpenes / toxicity
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / isolation & purification
Enzyme Inhibitors / toxicity
Humans
Insulin / metabolism
Japan
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Phosphorylation / drug effects
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism*
Pyrroles / chemistry
Signal Transduction / drug effects

Substances

Alkaloids
Diterpenes
Enzyme Inhibitors
Insulin
Pyrroles
Protein Tyrosine Phosphatase, Non-Receptor Type 1