Actinophyllic acid, a potent indole alkaloid inhibitor of the coupled enzyme assay carboxypeptidase u/hippuricase from the leaves of Alstonia actinophylla (Apocynaceae)

Bioassay-guided fractionation of the aqueous extract of the leaves of Alstonia actinophylla with use of a coupled enzyme assay, CPU/hippuricase, to detect carboxypeptidase U inhibitors led to the isolation of a novel indole alkaloid, actinophyllic acid (1). The structure of 1 was determined from detailed 2D NMR studies. Actinophyllic acid was found to be a potent inhibitor of the coupled enzyme assay with an IC(50) of 0.84 microM. Actinophyllic acid possesses a unique 2,3,6,7,9,13c-hexahydro-1H-1,7,8-(methanetriyloxymethano)pyrrolo1',2':1,2]azocino4,3-b]indole-8(5H)-carboxylic acid skeleton.