Verruculides A and B, two new protein tyrosine phosphatase 1B inhibitors from an Indonesian ascidian-derived Penicillium verruculosum

Bioorg Med Chem Lett. 2015 Aug 15;25(16):3087-90. doi: 10.1016/j.bmcl.2015.06.026. Epub 2015 Jun 14.

Abstract

Two new merosesquiterpenes, verruculides A (1) and B (2), were isolated from a culture broth of the Indonesian ascidian-derived Penicillium verruculosum TPU1311, together with three known congeners, chrodrimanins A (3), B (4), and H (5). The structures of 1 and 2 were assigned on the basis of their spectroscopic data (1D and 2D NMR, HRMS, UV, CD, and IR). Compound 2 had a linear sesquiterpene moiety and was considered to be the derivative of the biosynthetic precursor for 1 and 3-5. Compounds 1, 3, and 5 inhibited the activity of protein tyrosine phosphatase 1B (PTP1B) with IC50 values of 8.4, 8.5, and 14.9 μM, respectively. Compound 2 showed 40% inhibition at 23.1 μM, while 4 was not active at 20.7 μM.

Keywords: Ascidian-derived fungus; Inhibitor; Penicillium verruculosum; Protein tyrosine phosphatase 1B; Verruculide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / isolation & purification
  • Indonesia
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Penicillium / chemistry*
  • Penicillium / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Sesquiterpenes / chemistry*
  • Sesquiterpenes / isolation & purification
  • Urochordata / microbiology*

Substances

  • Enzyme Inhibitors
  • Sesquiterpenes
  • verruculide A
  • verruculide B
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1