Cryptocaryols A-H, α-pyrone-containing 1,3-polyols from Cryptocarya sp. implicated in stabilizing the tumor suppressor Pdcd4

  • J Nat Prod. 2011 May 27;74(5):1015-20. doi: 10.1021/np100918z.
Tanja Grkovic  1 ,  Johanna S Blees ,  Nancy H Colburn ,  Tobias Schmid ,  Cheryl L Thomas ,  Curtis J Henrich ,  James B McMahon ,  Kirk R Gustafson
Affiliations
  • 1. Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, United States.
PMID: 21539301 DOI: 10.1021/np100918z
Abstract

A high-throughput cell-based reporter assay designed to identify small-molecule stabilizers of the tumor suppressor Pdcd4 was used to screen extracts in the NCI Natural Products Repository. Bioassay-guided fractionation of an extract from a Papua New Guinea collection of the tropical tree Cryptocarya sp. provided a series of new 5,6-dihydro-α-pyrone-containing 1,3-polyols (1-8), named cryptocaryols A-H. Their structures were assigned from a combination of NMR, MS, and CD studies in conjunction with NMR database comparisons. Compounds 1-8 were found to rescue Pdcd4 from TPA-induced degradation with EC50 concentrations that ranged from 1.3 to 4.9 μM.