Microbial transformation of (-)-isolongifolol and butyrylcholinesterase inhibitory activity of transformed products

The microbial transformation of (-)-isolongifolol (1) by using the standard two-stage fermentation technique with Fusarium lini afforded polar oxygenated metabolites: 10-oxoisolongifolol (2), 10 alpha-hydroxyisolongifolol (3), and 9 alpha-hydroxyisolongifolol (4). Metabolites 3 and 4 were also formed with the incubation of 1 with Aspergillus niger. All three metabolites were found to be new. Compounds 3 and 4 inhibited butyrylcholinesterase enzyme in a concentration-dependent manner with IC50 values 13.6 and 299.5 mu M, respectively. Compound 3 showed un-competitive mode of inhibition against butyrylcholinesterase with K-i value 15.0 mu M. The structures of metabolites 2-4 were deduced on the basis of spectroscopic techniques and single-crystal X-ray diffraction techniques. (c) 2005 Elsevier Ltd. All rights reserved.