The synthesis and biological activity of novel anthracenone-pyranones and anthracenone-furans. Issue 13 (1st July 2015)

• Record Type: Journal Article
• Authors: Rixson, James E.; Abraham, James R.; Egoshi, Yuki; Skelton, Brian W.; Young, Kelly; Gilbert, Jayne; Sakoff, Jennette A.; Gericke, Kersten M.; McCluskey, Adam; Stewart, Scott G.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 13(2015)
• Page Start: 3552
• Page End: 3565
• Publication Date: 2015-07-01
• Subjects: Anthrapyranones -- Natural products -- Growth inhibition -- Human cancer cells -- Castro–Stephens reaction; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.04.032
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: An efficient and divergent methodology for the synthesis of new anthracenone-pyranones and anthracenone-furans is described as well as in vitro growth inhibition in a range of human cancer cells. The lead natural product BE-26554A displayed good cell growth activity on BE2-C neuroblastoma and SMA glioblastoma cell lines at 0.17, 0.16 μM (GI50 ), respectively. A CF3 functionalised anthracenone 4-pyranone (chromone) and an anthracenone-furan derivative which both displayed strong growth inhibition in the BE2-C neuroblastoma cell line are also discussed. 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 0.16 μM (GI50 ), respectively. Of note, were a CF3 functionalised anthracenone 4-pyranone (chromone) derivative22, and an anthracenone-furan derivative54 which displayed 0.20 μM and 0.38 μM growth inhibition, respectively, in the BE2-C neuroblastoma cell line.