Original Vinca Derivatives: From P-Glycoprotein Substrates to P-Glycoprotein Inhibitors

  • J Med Chem. 2016 Dec 8;59(23):10774-10780. doi: 10.1021/acs.jmedchem.6b00525.
Olga Gherbovet  1 ,  María Concepción García Alvarez  1 ,  Jérôme Bignon  1 ,  Fanny Roussi  1
Affiliations
  • 1. Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, UPR 2301 du CNRS, Université Paris-Saclay , 1 Avenue de la Terrasse, 91198, Gif-sur-Yvette Cedex, France.
PMID: 27753480 DOI: 10.1021/acs.jmedchem.6b00525
Abstract

The first example of vinca derivatives 16-18 able to modulate P-glycoprotein (Pgp) efflux activity is reported. They were elaborated in two steps from vinorelbine 3 (VLN) by a modification of the velbenamine moiety. These compounds were able to decrease efficiently Pgp mediated influx and efflux of rhodamine-123 (Rho) and to restore the cytotoxicity of vinorelbine 3 (VLN) and doxorubicin (Dox) on K562R (dox-resistant) cell lines.