title: Synthesis of migrastatin and its macroketone analogue and in vivo FRAP analysis of the macroketone on E-cadherin dynamics.
abstract: An efficient and scalable synthesis of a key acyclic intermediate used for the preparation of migrastatin and its macroketone analogue is described; Brown alkoxyallylation is the key step for this synthesis. The macroketone was prepared on 100 mg scale by this route. Treatment of invasive pancreatic cancer cells grown on a cell-derived matrix or as subcutaneous tumours in nude mice with the macroketone inhibited E-cadherin dynamics in a manner consistent with increased cell adhesion and reduced invasive potential.
authors.affiliation: School of Chemistry, National University of Ireland, Galway, University Road, Galway (Ireland).
authors.forename: Daniele
authors.initials: D
authors.lastname: Lo Re
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Max
authors.initials: M
authors.lastname: Nobis
authors.forename: Kurt I
authors.initials: KI
authors.lastname: Anderson
authors.forename: Paul V
authors.initials: PV
authors.lastname: Murphy
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D015820:Cadherins / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010881:Piperidones / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D018942:Macrolides; D010881:Piperidones; C418199:migrastatin
keywords: E-cadherin; antiproliferation; cell adhesion; cell-migration inhibitors; photobleaching