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

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...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Journal of medicinal chemistry 2016-12, Vol.59 (23), p.10774-10780
Hauptverfasser:	Gherbovet, Olga, García Alvarez, María Concepción, Bignon, Jérôme, Roussi, Fanny
Format:	Artikel
Sprache:	eng
Schlagworte:	ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors Cell Survival - drug effects Cells, Cultured Dose-Response Relationship, Drug Doxorubicin - chemistry Doxorubicin - isolation & purification Doxorubicin - pharmacology Humans K562 Cells Molecular Structure Rhodamine 123 - chemistry Rhodamine 123 - isolation & purification Rhodamine 123 - pharmacology Structure-Activity Relationship Vinblastine - analogs & derivatives Vinblastine - chemistry Vinblastine - isolation & purification Vinblastine - pharmacology Vinca - chemistry
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	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.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/acs.jmedchem.6b00525