title: Synthesis and Biological Investigation of Δ(12)-Prostaglandin J3 (Δ(12)-PGJ3) Analogues and Related Compounds.
abstract: A series of Δ(12)-prostaglandin J3 (Δ(12)-PGJ3) analogues and derivatives were synthesized employing an array of synthetic strategies developed specifically to render them readily available for biological investigations. The synthesized compounds were evaluated for their cytotoxicity against a number of cancer cell lines, revealing nanomolar potencies for a number of them against certain cancer cell lines. Four analogues (2, 11, 21, and 27) demonstrated inhibition of nuclear export through a covalent addition at Cys528 of the export receptor Crm1. One of these compounds (i.e., 11) is currently under evaluation as a potential drug candidate for the treatment of certain types of cancer. These studies culminated in useful and path-pointing structure-activity relationships (SARs) that provide guidance for further improvements in the biological/pharmacological profiles of compounds within this class.
authors.affiliation: Department of Chemistry, BioScience Research Collaborative, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: K C
authors.initials: KC
authors.lastname: Nicolaou
authors.affiliation: Department of Chemistry, BioScience Research Collaborative, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Pulukuri
authors.affiliation: Department of Chemistry, BioScience Research Collaborative, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Stephan
authors.initials: S
authors.lastname: Rigol
authors.affiliation: Department of Chemistry, BioScience Research Collaborative, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Philipp
authors.initials: P
authors.lastname: Heretsch
authors.affiliation: Department of Chemistry, BioScience Research Collaborative, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Ruocheng
authors.initials: R
authors.lastname: Yu
authors.affiliation: Department of Chemistry, BioScience Research Collaborative, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Charles I
authors.initials: CI
authors.lastname: Grove
authors.affiliation: Department of Chemistry, BioScience Research Collaborative, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Christopher R H
authors.initials: CR
authors.lastname: Hale
authors.affiliation: Department of Chemistry, BioScience Research Collaborative, Rice University , 6100 Main Street, Houston, Texas 77005, United States.
authors.forename: Abdelatif
authors.initials: A
authors.lastname: ElMarrouni
authors.affiliation: Department of Chemical Biology, Helmholtz Centre for Infection Research , Inhoffenstraße 7, 38124 Braunschweig, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Fetz
authors.affiliation: Department of Chemical Biology, Helmholtz Centre for Infection Research , Inhoffenstraße 7, 38124 Braunschweig, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Brönstrup
authors.affiliation: Stemcentrx Inc. , 450 East Jamie Court, South San Francisco, California 94080, United States.
authors.forename: Monette
authors.initials: M
authors.lastname: Aujay
authors.affiliation: Stemcentrx Inc. , 450 East Jamie Court, South San Francisco, California 94080, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Sandoval
authors.affiliation: Stemcentrx Inc. , 450 East Jamie Court, South San Francisco, California 94080, United States.
authors.forename: Julia
authors.initials: J
authors.lastname: Gavrilyuk
mesh_terms: D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015230:Prostaglandin D2 / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C499810:delta(12)-prostaglandin J(2); D015230:Prostaglandin D2