Actinophyllic Acid, a Potent Indole Alkaloid Inhibitor of the Coupled Enzyme Assay Carboxypeptidase U/Hippuricase from the Leaves of Alstonia actinophylla (Apocynaceae)

Abstract

Bioassay-guided fractionation of the acquous extract of the leaves of Alstonia actinophylla with use of a coupled enzyme assay, CPU/hippuricase, to detect carboxypeptidas 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 IC50 of 0.84 uM. Actinophyllic acid possesses a unique 2,3,6,7,9,13c-hexahydro-1H-1,7,8-(methanetriyloxymethano)-pyrrolo [1'm2':1,2] azocino [4,3-b] indole-8(5H)carboxylic acid skeleton.