title: Design, synthesis, and biological evaluation of conformationally constrained analogues of naphthol AS-E as inhibitors of CREB-mediated gene transcription.
abstract: Cyclic AMP response element binding protein (CREB) is often dysregulated in cancer cells and is an attractive cancer drug target. Previously, we described naphthol AS-E (1) as a small molecule inhibitor of CREB-mediated gene transcription. To understand its bioactive conformation, a series of conformationally constrained analogues of 1 were designed and synthesized. Biological evaluation of these analogues suggests that the global energy minimum of 1 is the likely bioactive conformation.
authors.affiliation: Program in Chemical Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.forename: Bingbing X
authors.initials: BX
authors.lastname: Li
authors.forename: Fuchun
authors.initials: F
authors.lastname: Xie
authors.forename: Frances
authors.initials: F
authors.lastname: Delaney
authors.forename: Xiangshu
authors.initials: X
authors.lastname: Xiao
mesh_terms: D000818:Animals; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors*; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D049410:Luciferases, Renilla / Q000378:metabolism; D008968:Molecular Conformation; D009284:Naphthols / Q000138:chemical synthesis* / Q000494:pharmacology; D055672:Static Electricity; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009284:Naphthols; C573561:naphthol AS-E; D049410:Luciferases, Renilla