Norterpene Cyclic Peroxides from the Marine Sponge Diacarnus spinipoculum, Inhibitors of Transient Receptor Potential Ankyrin 1

J Nat Prod. 2024 Feb 23;87(2):358-364. doi: 10.1021/acs.jnatprod.3c01104. Epub 2024 Feb 6.

Abstract

Bioassay-guided isolation of the extract from the marine sponge Diacarnus spinipoculum showing inhibitory activity against human transient receptor potential ankyrin 1 (hTRPA1) resulted in the isolation of 12 norditerpene cyclic peroxides (1-12) and eight norsesterterpene cyclic peroxides (13-20). Among these, 10 (5-7, 11, 12, 16-20) are unprecedented analogs. Compounds with either a hydroxy (5, 11) or a methoxy (6, 12) group attached to the cyclohexanone moiety were obtained as epimeric mixtures at C-11, while compounds 4, 6, 10, and 12 are likely the artifacts of isolation. The absolute configurations of the new compounds were established based on an NMR-based empirical method and comparison of specific rotation values. Mosher ester analysis revealed the absolute configurations of compounds 17-20. The inhibitory activity of the isolated compounds against hTRPA1 varied significantly depending on their structures, with the norsesterterpenoid 19 displaying the most potent activity (IC50 2.0 μM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ankyrins / antagonists & inhibitors
  • Diterpenes*
  • Humans
  • Molecular Structure
  • Peroxides / chemistry
  • Peroxides / pharmacology
  • Porifera* / chemistry
  • Terpenes / chemistry
  • Terpenes / pharmacology

Substances

  • Ankyrins
  • Diterpenes
  • Peroxides
  • Terpenes