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.
Yeonwoo Cho  1  2 ,  Chinmayee Bawkar  1  2 ,  Jung Mi Hyun  3 ,  Myung Jin Song  3 ,  Kwiwan Jeong  3 ,  Yeon-Ju Lee  1  2
Affiliations
  • 1. Marine Natural Products Chemistry Laboratory, Korea Institute of Ocean Science and Technology, Busan 49111, Republic of Korea.
  • 2. Department of Marine Technology and Convergence Engineering, University of Science and Technology, Daejeon 34113, Republic of Korea.
  • 3. Gyeonggido Business and Science Accelerator, 107 Gwanggyoro, Suwon 16229, Republic of Korea.
PMID: 38320400 DOI: 10.1021/acs.jnatprod.3c01104
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).

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