Hyrtioreticulins A-E, indole alkaloids inhibiting the ubiquitin-activating enzyme, from the marine sponge Hyrtios reticulatus

Bioorg Med Chem. 2012 Jul 15;20(14):4437-42. doi: 10.1016/j.bmc.2012.05.044. Epub 2012 May 24.

Abstract

Hyrtioreticulins A-E (1-5) were isolated from the marine sponge Hyrtios reticulatus, along with a known alkaloid, hyrtioerectine B (6). Structural elucidation on the basis of spectral data showed that 1, 2, and 5 are new tetrahydro-β-carboline alkaloids, while 3 and 4 are new azepinoindole-type alkaloids. Hyrtioreticulins A and B (1 and 2) inhibited ubiquitin-activating enzyme (E1) with IC(50) values of 0.75 and 11μg/mL, respectively, measured by their inhibitory abilities against the formation of an E1-ubiquitin intermediate. So far, only five E1 inhibitors, panapophenanthrine, himeic acid A, largazole, and hyrtioreticulins A and B (1 and 2), have been isolated from natural sources and, among them, 1 is the most potent E1 inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / metabolism
  • Indole Alkaloids / chemistry*
  • Indole Alkaloids / isolation & purification
  • Indole Alkaloids / metabolism
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Porifera / chemistry*
  • Ubiquitin-Activating Enzymes / antagonists & inhibitors*
  • Ubiquitin-Activating Enzymes / metabolism

Substances

  • Enzyme Inhibitors
  • Indole Alkaloids
  • hyrtioerectine B
  • Ubiquitin-Activating Enzymes