Marine sponge Bis(Indole) alkaloids that displace ligand binding to α1 adrenergic receptors

The α1 adrenergic receptor assay guided fractionation of an extract from the marine sponge Spongosorites sp. led to the isolation of topsentin-B2 (bromotopsentin) as the active compound. Topsentin-B2 and five related bis(indole) marine sponge metabolites were shown to displace ligand binding to α1a and α1b adrenergic receptors with Ki values for the α1b receptor ranging from 0.08 to 1.15 μM. All six compounds show selectivity for α1b relative to α1a adrenergic receptors. Marine sponge bis(indole) alkaloids such as topsentin-B2 (1) were shown to displace ligand binding to α1 adrenergic receptors. Six marine sponge derived bis(indoles) preferentially displaced ligand binding to α1b over α 1a adrenergic receptors with α1b Ki values ranging from 0.08 to 1.15 μM.