title: Synthesis, anti-cancer and anti-inflammatory activity of novel 2-substituted isoflavenes.
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.
authors.affiliation: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Eiffe
authors.affiliation: 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.
authors.forename: Eddy
authors.initials: E
authors.lastname: Pasquier
authors.affiliation: 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.
authors.forename: Maria
authors.initials: M
authors.lastname: Kavallaris
authors.affiliation: School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Cristan
authors.initials: C
authors.lastname: Herbert
authors.affiliation: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: David
authors.initials: D
authors.lastname: StC Black
authors.affiliation: School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: n.kumar@unsw.edu.au.
authors.forename: Naresh
authors.initials: N
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D000093242:Interleukin-6 Inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D005419:Flavonoids; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000093242:Interleukin-6 Inhibitors
keywords: Anti-cancer; Anti-inflammatory; Isoflavene; Isoflavonoid; Isoflavylium; Nucleophilic addition