Sinularamides A-G, Terpenoid-Derived Spermidine and Spermine Conjugates with Casitas B-Lineage Lymphoma Proto-Oncogene B (Cbl-b) Inhibitory Activities from a Sinularia sp. Soft Coral

J Nat Prod. 2021 Jun 25;84(6):1831-1837. doi: 10.1021/acs.jnatprod.1c00367. Epub 2021 May 26.

Abstract

An extract of a Sinularia sp. soft coral showed inhibitory activity against the E3-ubiquitin ligase casitas B-lineage lymphoma proto-oncogene B (Cbl-b). Subsequent bioassay-guided separation of the extract provided a series of terpenoid-derived spermidine and spermine amides that were named sinularamides A-G (1-7). Compounds 1-7 represent new natural products; however, sinularamide A (1) was previously reported as a synthetic end product. The structures of sinularamides A-G (1-7) were elucidated by analysis of spectroscopic and spectrometric data from NMR, IR, and HRESIMS experiments and by comparison with literature data. All of the isolated compounds showed Cbl-b inhibitory activities with IC50 values that ranged from approximately 6.5 to 33 μM.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors*
  • Animals
  • Anthozoa / chemistry*
  • Molecular Structure
  • Palau
  • Proto-Oncogene Proteins c-cbl / antagonists & inhibitors*
  • Spermidine / isolation & purification
  • Spermidine / pharmacology*
  • Spermine / isolation & purification
  • Spermine / pharmacology*
  • Terpenes / isolation & purification
  • Terpenes / pharmacology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Terpenes
  • Spermine
  • CBLB protein, human
  • Proto-Oncogene Proteins c-cbl
  • Spermidine