Semisynthesis of α-methyl-γ-lactones and in vitro evaluation of their activity on protein farnesyltransferase

Abstract

The semisynthesis of xanthanolide derivatives is reported from xanthinin and 4-epi-isoxanthanol, two sesquiterpene lactones isolated from the crude chloroformic extract of the leaves of Xanthium macrocarpum DC. (Asteraceae) by liquid/liquid chromatography. In vitro evaluation of their protein farnesyltransferase (PFTase) inhibitory activity has been investigated. In contrast to other biological activities of xanthanolides, PFTase inhibition is not associated with the presence of the potentially toxic α-methylene-γ-lactone function.

Keywords::

• Protein farnesyltransferase inhibitors
• sesquiterpene lactone
• xanthanolide
• semisynthesis

Acknowledgements

We are grateful to Kromaton Technologies (Angers, France) for FCPC access, Dr Denis Lesage (LCSOB, UMR 7613, Université Pierre et Marie Curie, Paris VI, France) for HRMS Orbitrap access, David Rondeau (Service commun d’analyses spectroscopiques, Université d’Angers, France) for MS analysis, and Jean-Bernard Créchet (ICSN-CNRS, Gif sur Yvette, France) for the generous gift of the E. Coli strain expressing yeast PFTase and to Dr Jamal Ouazzani and Sylvie Cortial for its production and isolation.

Declaration of interest

This research was supported by a grant from the “Région des Pays de la Loire.” The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.