title: Cryptocaryols A-H, α-pyrone-containing 1,3-polyols from Cryptocarya sp. implicated in stabilizing the tumor suppressor Pdcd4.
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.
authors.affiliation: Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, United States.
authors.forename: Tanja
authors.initials: T
authors.lastname: Grkovic
authors.forename: Johanna S
authors.initials: JS
authors.lastname: Blees
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Colburn
authors.forename: Tobias
authors.initials: T
authors.lastname: Schmid
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Thomas
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Henrich
authors.forename: James B
authors.initials: JB
authors.lastname: McMahon
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Gustafson
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000187:drug effects* / Q000378:metabolism; D031369:Cryptocarya / Q000737:chemistry*; D016147:Genes, Tumor Suppressor; D015394:Molecular Structure; D054547:National Cancer Institute (U.S.); D019906:Nuclear Magnetic Resonance, Biomolecular; D010219:Papua New Guinea; D011108:Polymers / Q000737:chemistry*; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D016601:RNA-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D014481:United States
chemical_list: D051017:Apoptosis Regulatory Proteins; C114487:PDCD4 protein, human; D011108:Polymers; D011753:Pyrones; D016601:RNA-Binding Proteins; C024617:polyol