Inhibitory Activity on Binding of Specific Ligands to the Human Angiotensin II AT1and Endothelin 1 ETAReceptors: Bioactive Benzo[c]phenanthridine Alkaloids from the Root ofBocconia frutescens

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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.