Activity-guided isolation of an antiandrogenic compound of Pygeum africanum.
Inactivation of the androgen receptor (AR) through androgen ablation and treatment with antiandrogens is a major goal in the therapy for prostate hyperplasia and prostate cancer. Bioactivity-directed fractionation of a selective dichloromethane extract from the stem bark of Pygeum africanum led to the isolation of the antiandrogenic compound atraric acid. Its activity was examined by an androgen receptor responsive reporter gene assay. For lead structure optimization we transformed the natural occurring compound atraric acid into its ethyl, N-propyl and N-butyl esters and their antiandrogenic activities were examined as well. In addition, benzoic acid was isolated. The structures of all compounds were determined and characterized by means of 1H- and 13C-NMR, HR-EI-mass, IR and UV spectroscopy.
Schleich
Sonja
S
Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, Marburg, Germany.
Papaioannou
Maria
M
Baniahmad
Aria
A
Matusch
Rudolf
R
D000726:Androgen Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006801:Humans; D062385:Hydroxybenzoates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy; D000068218:Prunus africana; D011944:Receptors, Androgen / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000726:Androgen Antagonists; D062385:Hydroxybenzoates; D010936:Plant Extracts; D011944:Receptors, Androgen; C480398:atraric acid