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)pyrrolo[1',2':1,2]azocino[4,3-b]indole-8(5H)-carboxylic acid skeleton.
Carroll
Anthony R
AR
Natural Product Discovery, Eskitis Institute, Griffith University, Brisbane, Australia 4111. a.carroll@griffith.edu.au
Hyde
Edward
E
Smith
Jill
J
Quinn
Ronald J
RJ
Guymer
Gordon
G
Forster
Paul I
PI
D031051:Alstonia / Q000737:chemistry*; D000581:Amidohydrolases / Q000737:chemistry*; D001681:Biological Assay; D025901:Carboxypeptidase B2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry / Q000201:enzymology
D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; C500686:actinophyllic acid; D025901:Carboxypeptidase B2; D000581:Amidohydrolases; C019672:aminoacylase I