The synthesis and biological activity of novel anthracenone-pyranones and anthracenone-furans

James E Rixson; James R Abraham; Yuki Egoshi; Brian W Skelton; Kelly Young; Jayne Gilbert; Jennette A Sakoff; Kersten M Gericke; Adam McCluskey; Scott G Stewart

doi:10.1016/j.bmc.2015.04.032

The synthesis and biological activity of novel anthracenone-pyranones and anthracenone-furans

Bioorg Med Chem. 2015 Jul 1;23(13):3552-65. doi: 10.1016/j.bmc.2015.04.032. Epub 2015 Apr 22.

Authors

Affiliations

¹ The School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia.
² 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.
³ Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Crawley, WA 6009, Australia.
⁴ Department of Medical Oncology, Calvary Mater Newcastle Hospital, Edith Street, Waratah, 2298 NSW, Australia.
⁵ Bayer Pharma AG, Medicinal Chemistry, 42096 Wuppertal, Germany.
⁶ Chemistry Building, The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia. Electronic address: Adam.McCluskey@newcastle.edu.au.
⁷ The School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA 6009, Australia. Electronic address: scott.stewart@uwa.edu.au.

PMID: 25979375
DOI: 10.1016/j.bmc.2015.04.032

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.

Keywords: Anthrapyranones; Castro–Stephens reaction; Growth inhibition; Human cancer cells; Natural products.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anthracenes / chemical synthesis*
Anthracenes / pharmacology
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology
Binding Sites
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
Chromones / chemical synthesis*
Chromones / pharmacology
Drug Design
Drug Screening Assays, Antitumor
Furans / chemical synthesis*
Furans / pharmacology
Humans
Inhibitory Concentration 50
Molecular Structure
Neuroglia / drug effects
Neuroglia / pathology
Neurons / drug effects
Neurons / pathology
Protein Binding
Structure-Activity Relationship

Substances

Anthracenes
Antineoplastic Agents
Chromones
Furans