title: Synthesis of rocaglamide hydroxamates and related compounds as eukaryotic translation inhibitors: synthetic and biological studies.
abstract: The rocaglates/rocaglamides are a class of natural products known to display potent anticancer activity. One such derivative, silvestrol, has shown activity comparable to taxol in certain settings. Here, we report the synthesis of various rocaglamide analogues and identification of a hydroxamate derivative (-)-9 having activity similar to silvestrol in vitro and ex vivo for inhibition of protein synthesis. We also show that (-)-9 synergizes with doxorubicin in vivo to reduce Eμ-Myc driven lymphomas.
authors: Department of Chemistry, Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States.
authors: Christina M
authors: CM
authors: Rodrigo
authors: Regina
authors: R
authors: Cencic
authors: Stéphane P
authors: SP
authors: Roche
authors: Jerry
authors: J
authors: Pelletier
authors: John A
authors: JA
authors: Porco
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D039562:Eukaryotic Initiation Factor-4F / Q000037:antagonists & inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000378:metabolism; D021122:Protein Subunits / Q000037:antagonists & inhibitors; D011500:Protein Synthesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D039562:Eukaryotic Initiation Factor-4F; D006877:Hydroxamic Acids; C570924:N-methoxy rocaglamide; D021122:Protein Subunits; D011500:Protein Synthesis Inhibitors; D014315:Triterpenes; C489897:silvestrol; D004317:Doxorubicin; C107772:rocaglamide