Biotransformations of imbricatolic acid by Aspergillus niger and Rhizopus nigricans cultures.
Microbial transformation of imbricatolic acid (1) by Aspergillus niger afforded 1alpha-hydroxyimbricatolic acid (2), while transformation with Rhizopus nigricans yielded 15-hydroxy-8,17-epoxylabdan-19-oic acid (3). When the diterpene 1 was added to a Cunninghamella echinulata culture, the main products were the microbial metabolites mycophenolic acid (4) and its 3-hydroxy derivative 5. All the structures were elucidated by spectroscopic methods. The cytotoxicity of these compounds towards human lung fibroblasts and AGS cells was assessed. While 4 and 5 showed low cytotoxicity, with IC50 values > 1000 microM against AGS cells and fibroblasts, 1alpha-hydroxyimbricatolic acid (2) presented moderate toxicity towards these targets, with IC50 values of 307 and 631 microM, respectively. The structure of 2 is presented for the first time.
Schmeda-Hirschmann
Guillermo
G
Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile. schmeda@utalca.cl
Aranda
Carlos
C
Kurina
Marcela
M
Rodríguez
Jaime A
JA
Theoduloz
Cristina
C
D001234:Aspergillus niger / Q000378:metabolism*; D001711:Biotransformation; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012233:Rhizopus / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
D004224:Diterpenes; C524691:imbricatolic acid