title: The synthesis and biological activity of novel anthracenone-pyranones and anthracenone-furans.
abstract: An efficient and divergent methodology for the synthesis of new anthracenone-pyranones and anthracenone-furans is described. Key reactions discussed in these syntheses include an aldehyde promoted annulation with a β-keto-sulfoxide, a domino alkyne insertion/carbonylation/Nu-acylation and a DMEDA promoted Castro-Stephens reaction. We also report the in vitro growth inhibition of these compounds in a range of human cancer cells. The natural product BE-26554A displayed good cell growth activity on BE2-C neuroblastoma and SMA glioblastoma cell lines at 0.17 and 0.16μM (GI50), respectively. Of note, were a CF3 functionalised anthracenone 4-pyranone (chromone) derivative 22, and an anthracenone-furan derivative 54 which displayed 0.20μM and 0.38μM growth inhibition, respectively, in the BE2-C neuroblastoma cell line.
authors.affiliation: The School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.
authors.forename: James E
authors.initials: JE
authors.lastname: Rixson
authors.affiliation: The School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.
authors.forename: James R
authors.initials: JR
authors.lastname: Abraham
authors.affiliation: The School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia; Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, 7-1 Kioicho, Chiyoda-ku, Tokyo 102-8554, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Egoshi
authors.affiliation: Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Crawley, WA 6009, Australia.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Skelton
authors.affiliation: Department of Medical Oncology, Calvary Mater Newcastle Hospital, Edith Street, Waratah, 2298 NSW, Australia.
authors.forename: Kelly
authors.initials: K
authors.lastname: Young
authors.affiliation: Department of Medical Oncology, Calvary Mater Newcastle Hospital, Edith Street, Waratah, 2298 NSW, Australia.
authors.forename: Jayne
authors.initials: J
authors.lastname: Gilbert
authors.affiliation: Department of Medical Oncology, Calvary Mater Newcastle Hospital, Edith Street, Waratah, 2298 NSW, Australia.
authors.forename: Jennette A
authors.initials: JA
authors.lastname: Sakoff
authors.affiliation: Bayer Pharma AG, Medicinal Chemistry, 42096 Wuppertal, Germany.
authors.forename: Kersten M
authors.initials: KM
authors.lastname: Gericke
authors.affiliation: Chemistry Building, The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia. Electronic address: Adam.McCluskey@newcastle.edu.au.
authors.forename: Adam
authors.initials: A
authors.lastname: McCluskey
authors.affiliation: The School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia. Electronic address: scott.stewart@uwa.edu.au.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Stewart
mesh_terms: D000873:Anthracenes / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000138:chemical synthesis* / Q000494:pharmacology; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D002867:Chromones; D005663:Furans
keywords: Anthrapyranones; Castro–Stephens reaction; Growth inhibition; Human cancer cells; Natural products