title: Discovery and preliminary SAR of bisbenzylisoquinoline alkaloids as inducers of C/EBPα.
abstract: A high throughput in vitro screen has been developed to identify substances that induce expression of C/EBPα in tumor cells. An extract of the fruit of Gyrocarpus jacquinii showed induction of C/EBPα activity that was attributed to the bisbenzylisoquinoline (BBIQ) alkaloid pheanthine (13) by dereplication analysis. The research project was broadened to assess the effect of other natural BBIQ structural types occurring outside the genus Gyrocarpus. Several of the 28 compounds assayed showed enhancement of C/EBPα induction in U937 cells. The results of this study should encourage future efforts toward obtaining and screening a larger set of both natural and synthetic analogs of this interesting group of alkaloids.
authors: Natural Products Support Group, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, USA. klausmeyerp@mail.nih.gov
authors: Paul
authors: P
authors: Klausmeyer
authors: Thomas G
authors: TG
authors: McCloud
authors: Dominic A
authors: DA
authors: Scudiero
authors: Michael J
authors: MJ
authors: Currens
authors: John H
authors: JH
authors: Cardellina Ii
authors: Robert H
authors: RH
authors: Shoemaker
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D005638:Fruit / Q000737:chemistry; D049935:Hernandiaceae / Q000737:chemistry; D057166:High-Throughput Screening Assays; D006801:Humans; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D022763:CCAAT-Enhancer-Binding Protein-alpha; D010936:Plant Extracts