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

Anthony R Carroll; Edward Hyde; Jill Smith; Ronald J Quinn; Gordon Guymer; Paul I Forster

doi:10.1021/jo048439n

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

J Org Chem. 2005 Feb 4;70(3):1096-9. doi: 10.1021/jo048439n.

Authors

Anthony R Carroll¹, Edward Hyde, Jill Smith, Ronald J Quinn, Gordon Guymer, Paul I Forster

Affiliation

¹ Natural Product Discovery, Eskitis Institute, Griffith University, Brisbane, Australia 4111. a.carroll@griffith.edu.au

PMID: 15675882
DOI: 10.1021/jo048439n

Abstract

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)pyrrolo[1',2':1,2]azocino[4,3-b]indole-8(5H)-carboxylic acid skeleton.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alstonia / chemistry*
Amidohydrolases / chemistry*
Biological Assay
Carboxypeptidase B2 / antagonists & inhibitors*
Carboxypeptidase B2 / chemistry
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / isolation & purification*
Enzyme Inhibitors / pharmacology
Indole Alkaloids / chemistry
Indole Alkaloids / isolation & purification*
Indole Alkaloids / pharmacology
Plant Leaves / chemistry
Plant Leaves / enzymology

Substances

Enzyme Inhibitors
Indole Alkaloids
actinophyllic acid
Carboxypeptidase B2
Amidohydrolases
aminoacylase I