1. Synthesis of migrastatin and its macroketone analogue and in vivo FRAP analysis of the macroketone on E-cadherin dynamics
- Author
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Kurt I. Anderson, Ying Zhou, Paul V. Murphy, Daniele Lo Re, Max Nobis, and ~
- Subjects
Migrastatin ,Mice, Nude ,Antineoplastic Agents ,Molecular dynamics ,Matrix (biology) ,Adenocarcinoma ,Gene ,Biochemistry ,Cell-migration inhibitors ,Wadsworth-emmons reaction ,chemistry.chemical_compound ,In vivo ,Cell Movement ,Pancreatic cancer ,medicine ,Cell Adhesion ,Tumor Cells, Cultured ,Animals ,Humans ,Macrolide core ,Cell adhesion ,Molecular Biology ,Piperidones ,Photobleaching ,Chemistry ,Cadherin ,Organic Chemistry ,Dynamics (mechanics) ,E-cadherin ,Antiproliferation ,medicine.disease ,Cadherins ,Cell biology ,Real time ,Pancreatic Neoplasms ,Potent inhibitors ,Molecular Medicine ,Ethyl (diarylphosphono) acetates ,Macrolides ,Tumor metastasis ,Fluorescence Recovery After Photobleaching - 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. Science Foundation Ireland (Grant Nos. 07/IN.1/B966 and 11/TIDA/B2047), People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement number PIEF-GA-2011-299042 peer-reviewed
- Published
- 2014