Synthesis of migrastatin analogues as inhibitors of tumour cell migration: exploring structural change in and on the macrocyclic ring
Santocanale, Corrado Leahy, Lorraine Jones, Leigh Zhou, Ling Murphy, Paul V.
Santocanale, Corrado
Leahy, Lorraine
Jones, Leigh
Zhou, Ling
Murphy, Paul V.
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Publication Date
2015-11-04
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Article
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Lo Re D, Zhou Y;Mucha J;Jones LF;Leahy L;Santocanale C;Krol M;Murphy PV (2015) 'Synthesis of migrastatin analogues as inhibitors of tumour cell migration: exploring structural change in and on the macrocyclic ring'. Chemistry (Weinheim an der Bergstrasse, Germany), .
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..
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Wiley
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Attribution-NonCommercial-NoDerivs 3.0 Ireland