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Synthesis of migrastatin analogues as inhibitors of tumour cell migration: exploring structural change in and on the macrocyclic ring
LoRe, D Zhou, Y Mucha, J Leahy, L Santocanale, C Krol, M Murphy, PV
LoRe, D
Zhou, Y
Mucha, J
Leahy, L
Santocanale, C
Krol, M
Murphy, PV
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2015-11-04
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Abstract
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. 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.
Citation
Lo Re, D., Zhou, Y., Mucha, J., Jones, L. F., Leahy, L., Santocanale, C., Krol, M. and Murphy, P. V. (2015). Synthesis of migrastatin analogues as inhibitors of tumour cell migration: exploring structural change in and on the macrocyclic ring. Chemistry - A European Journal, 21(50), pp. 18109-18121. https://doi.org/10.1002/chem.201502861
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PubMed ID
26561335
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Journal article
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en
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ISSN
0947-6539
EISSN
1521-3765
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This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co‐funded under the European Regional Development Fund under Grant Number 14/SP/2710. The research leading to these results has also received funding in part from the People Programme (Marie Curie Actions) of the European Union′s Seventh Framework Programme FP7/2007‐2013/ under REA grant agreement No. PIEF‐GA‐2011‐299042 and the Poland National Science Council.