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Planta Med 2002; 68(9): 770-775
DOI: 10.1055/s-2002-34406
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Inhibitory Activity on Binding of Specific Ligands to the Human Angiotensin II AT1 and Endothelin 1 ETA Receptors: Bioactive Benzo[c]phenanthridine Alkaloids from the Root of Bocconia frutescens

Catherina Caballero-George1 , Patrick M. L. Vanderheyden2 , Sandra Apers1 , Hilde Van den Heuvel1 , Pablo N. Solis3 , Mahabir P. Gupta3 , Magda Claeys1 , Luc Pieters1 , Georges Vauquelin2 , Arnold J. Vlietinck1
  • 1Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium
  • 2Department of Molecular and Biochemical Pharmacology, Free University of Brussels (VUB), St.Genesius-Rode, Belgium
  • 3Center for Pharmacognostic Research on Panamanian Flora (CIFLORPAN), School of Pharmacy, University of Panama, Panama, Panama
Further Information

Publication History

Received: December 10, 2001

Accepted: April 7, 2002

Publication Date:
30 September 2002 (online)

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Abstract

A bioassay-guided fractionation of the 80 % ethanolic extract from Bocconia frutescens L. roots, showing a dose-dependent inhibitory effect towards both [3 H]-angiotensin II and [3 H]-BQ-123 binding to the human angiotensin II AT1 and endothelin 1 ETA receptors, led to an alkaloidal subfraction as the only responsible fraction for the activity of the whole extract. Among the alkaloids present in this fraction sanguinarine and chelerythrine were significant inhibitors of [3 H]-angiotensin II binding (hAT1 receptor), with IC50 values within the micromolar range. On the contrary, the [3 H]-BQ-123 binding (ETA receptor) was only weakly inhibited. Moreover, other members of the isoquinoline alkaloid family such as chelidonine and some protoberberine alkaloids exhibited no affinity for the two receptors. The present work shows the possible structure-activity relationship for these benzophenanthridine alkaloids on a screening bioassay using both stably transfected Chinese hamster ovary (CHO) and the human neuroblastoma SK-N-MC cells. Furthermore, the ability of these compounds to block AT1 and/or ETA receptors may provide some justification for the traditional use of Bocconia frutescens L. to control hypertension.

Key words

Bocconia frutescens - Papaveraceae - benzophenanthridine alkaloids - hAT1 receptor - ETA receptor - CHO cells - SK-N-MC cells

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Prof. Dr. A. J. Vlietinck

Department of Pharmaceutical Sciences

University of Antwerp (UIA)


Universiteitsplein-1,

2610, Antwerpen

Belgium

Email: vlietink@uia.ua.ac.be

Fax: +32 3820-2709