Abstract
Migrastatin and isomigrastatin analogues have been synthesised in order to contribute to structure-activity studies on tumour cell migration inhibitors. These include macrocycles varying in ring size, functionality and alkene stereochemistry, as well as glucuronides. The synthesis work included application of the Saegusa-Ito reaction for regio- and stereoselective unsaturated macroketone formation, diastereoselective Brown allylation to generate 9-methylmigrastatin analogues and chelation-induced anomerisation to vary glucuronide configuration. Compounds were tested in vitro against both breast and pancreatic cancer cell lines and inhibition of tumour cell migration was observed in both wound-healing (scratch) and Boyden chamber assays. One unsaturated macroketone showed low affinity for a range of secondary drug targets, indicating it is at low risk of displaying adverse side effects.
| Original language | English |
|---|---|
| Pages (from-to) | 18109-18121 |
| Number of pages | 13 |
| Journal | Chemistry - A European Journal |
| Volume | 21 |
| Issue number | 50 |
| DOIs | |
| Publication status | Published - 7 Dec 2015 |
Keywords
- anomerization
- glycosidation
- natural products
- stereoselective synthesis
- tumour cell migration
Authors (Note for portal: view the doc link for the full list of authors)
- Authors
- Lo Re, D. and Zhou, Y. and Mucha, J. and Jones, L. F. and Leahy, L. and Santocanale, C. and Krol, M. and Murphy, P. V.
