title: Horner-Wadsworth-Emmons approach to piperlongumine analogues with potent anti-cancer activity.
abstract: Natural products with anti-cancer activity play a vital role in lead and target discovery. We report here the synthesis and biological evaluation of the plant-derived alkaloid, piperlongumine and analogues. Using a Horner-Wadsworth-Emmons coupling approach, a selection of piperlongumine-like compounds were prepared in good overall yield from a novel phosphonoacetamide reagent. A number of the compounds displayed potent anti-cancer activity against colorectal (HCT 116) and ovarian (IGROV-1) carcinoma cell lines, via a mechanism of action which may involve ROS generation. Contrary to previous reports, no selective action in cancer cell (MRC-5) was observed for piperlongumine analogues.
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK. John.Moses@nottingham.ac.uk.
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Han
authors.forename: Paul A
authors.initials: PA
authors.lastname: Stanley
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Wood
authors.forename: Pallavi
authors.initials: P
authors.lastname: Sharma
authors.forename: Anchala I
authors.initials: AI
authors.lastname: Kuruppu
authors.forename: Tracey D
authors.initials: TD
authors.lastname: Bradshaw
authors.forename: John E
authors.initials: JE
authors.lastname: Moses
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004148:Dioxolanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D010881:Piperidones
chemical_list: D000970:Antineoplastic Agents; D004148:Dioxolanes; D017382:Reactive Oxygen Species; C498077:piperlongumine; D010881:Piperidones