Cytotoxicity and p-glycoprotein modulating effects of quinolones and indoloquinazolines from the Chinese herb Evodia rutaecarpa.

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 IC (50) values from 2.64 to 4.53 microM 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 microM.

journal_name

Planta Med

journal_title

Planta medica

authors

Adams M,Mahringer A,Kunert O,Fricker G,Efferth T,Bauer R

doi

10.1055/s-2007-993743

subject

Has Abstract

pub_date

2007-12-01 00:00:00

pages

1554-7

issue

15

eissn

0032-0943

issn

1439-0221

journal_volume

73

pub_type

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