Synthesis, anti-cancer and anti-inflammatory activity of novel 2-substituted isoflavenes

Eleanor Eiffe; Eddy Pasquier; Maria Kavallaris; Cristan Herbert; David StC Black; Naresh Kumar

doi:10.1016/j.bmc.2014.08.010

Synthesis, anti-cancer and anti-inflammatory activity of novel 2-substituted isoflavenes

Bioorg Med Chem. 2014 Oct 1;22(19):5182-93. doi: 10.1016/j.bmc.2014.08.010. Epub 2014 Aug 17.

Authors

Eleanor Eiffe¹, Eddy Pasquier², Maria Kavallaris³, Cristan Herbert⁴, David StC Black¹, Naresh Kumar⁵

Affiliations

¹ School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia.
² Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Randwick, NSW 2052, Australia; Metronomics Global Health Initiative, Marseille, France.
³ Children's Cancer Institute Australia for Medical Research, Lowy Cancer Research Centre, University of New South Wales, Randwick, NSW 2052, Australia; Australian Centre for Nanomedicine, School of Chemical Engineering, UNSW, Sydney, New South Wales 2052, Australia.
⁴ School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
⁵ School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: n.kumar@unsw.edu.au.

PMID: 25189689
DOI: 10.1016/j.bmc.2014.08.010

Abstract

Fifteen novel 2-substituted isoflavenes were synthesised via nucleophilic addition to isoflavylium salts. Twelve of the newly synthesised isoflavenes, along with the unsubstituted parent isoflavene, were tested in cell viability assays against the SHEP neuroblastoma and MDA-MB-231 breast adenocarcinoma cell lines. While the 2-substituted isoflavenes displayed a range of anti-proliferative activities, in most cases they were less active that the unsubstituted isoflavene (IC50=9.9 μM vs SHEP; IC50=33 μM vs MDA-MB-231). However, compound 7f, derived from the reaction between isoflavylium salt 5 and para-methoxyacetophenone, showed improved anti-proliferative activity against breast cancer cells (IC50=7.6 μM). Furthermore, compound 7f, as well as analogues 7a, 7c, 11d and 14, inhibited the production of interleukin-6 in LPS-activated RAW 264.7 cells.

Keywords: Anti-cancer; Anti-inflammatory; Isoflavene; Isoflavonoid; Isoflavylium; Nucleophilic addition.

Publication types

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

MeSH terms

Animals
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Flavonoids / chemical synthesis
Flavonoids / chemistry
Flavonoids / pharmacology*
Humans
Interleukin-6 / antagonists & inhibitors*
Interleukin-6 / biosynthesis
Lipopolysaccharides / antagonists & inhibitors
Lipopolysaccharides / pharmacology
Macrophages / drug effects
Macrophages / metabolism
Mice
Molecular Structure
Structure-Activity Relationship

Substances

Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents
Flavonoids
Interleukin-6
Lipopolysaccharides