Planta Med 2007; 73(15): 1554-1557
DOI: 10.1055/s-2007-993743
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Cytotoxicity and P-Glycoprotein Modulating Effects of Quinolones and Indoloquinazolines from the Chinese Herb Evodia rutaecarpa

Michael Adams1 , Anne Mahringer2 , Olaf Kunert1 , Gert Fricker2 , Thomas Efferth3 , Rudolf Bauer1
  • 1Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria
  • 2Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany
  • 3German Cancer Research Centre, Heidelberg, Germany
Further Information

Publication History

Received: July 13, 2007 Revised: October 13, 2007

Accepted: October 22, 2007

Publication Date:
06 December 2007 (online)

Abstract

The antimycobacterial quinolones 1-methyl-2-undecyl-4-quinolone, dihydroevocarpine and evocarpine as well as the indoloquinazoline alkaloids rutaecarpine and evodiamine - all from the Chinese medicinal herb Evodia rutaecarpa - were tested in two in vitro assays, for cytotoxicity and interaction with p-glycoprotein (p-gp). Cytotoxicity was measured in a cell proliferation assay against CCRF-CEM leukemia cells and their p-gp over-expressing subline CEM/ADR5000. An assay monitoring the p-gp-dependent accumulation of the dye calcein in porcine brain capillary endothelial cells (PBCECs) was used to study interactions of the test substances with this efflux pump. Rutaecarpine and evodiamine showed quite high toxicity with IC50 values from 2.64 to 4.53 μM and were weak modulators of p-gp activity. The degrees of resistance in CEM/ADR5000 towards the saturated quinolones 1-methyl-2-undecyl-4-quinolone and dihydroevocarpine were between 3 and 4. In the calcein assay, these two quinolones were shown to be moderate modulators of p-gp activity. Evocarpine, on the other side, is not transported by p-gp, and showed only slight toxicity at the highest test concentration of 30 μM.

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Prof. Dr. Rudolf Bauer

Institut für Pharmazeutische Wissenschaften

Abteilung für Pharmakognosie

Universitätsplatz

8010 Graz

Austria

Phone: +43-(0)316-380-8700

Fax: +43-(0)316-380-9860

Email: rudolf.bauer@uni-graz.at

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