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

Olga Gherbovet, María Concepción García Alvarez, Jérôme Bignon, Fanny Roussi
Journal of Medicinal Chemistry 2016 December 9
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.

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