Strongylophorines, new protein tyrosine phosphatase 1B inhibitors, from the marine sponge Strongylophora strongilata collected at Iriomote Island

Bioorg Med Chem Lett. 2015 Sep 15;25(18):3900-2. doi: 10.1016/j.bmcl.2015.07.039. Epub 2015 Jul 21.

Abstract

A new meroditerpene, 26-O-ethylstrongylophorine-14 (1), was isolated from the Okinawan marine sponge Strongylophora strongilata together with six known strongylophorines: 26-O-methylstrongylophorine-16 (2) and strongylophorines-2 (3), -3 (4), -8 (5), -15 (6), and -17 (7). The structure of 1 was assigned on the basis of its spectroscopic data. Compound 1 inhibited the activity of protein tyrosine phosphatase 1B (PTP1B) with an IC50 value of 8.7 μM, while known compounds 2-8 gave IC50 values of 8.5, >24.4, 9.0, 21.2, 11.9, and 14.8 μM, respectively. Oleanolic acid, a positive control, inhibited PTP1B activity at 0.7 μM (IC50). The inhibitory activities of strongylophorines possessing the acetal moiety at C-26 (1, 2, and 6) were stronger than those of the lactone derivatives (3 and 5). This is the first study to demonstrate that meroditerpenes inhibit PTP1B activity.

Keywords: Marine sponge; Meroditerpene; PTP1B inhibitor; Strongylophora strongilata; Strongylophorine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Islands
  • Molecular Conformation
  • Porifera / chemistry*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Diterpenes
  • Enzyme Inhibitors
  • PTPN1 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1