New AChE inhibitors from microbial transformation of trachyloban-19-oic acid by Syncephalastrum racemosum.

Trachyloban-19-oic acid (1) is a diterpene very abundant in nature and its structural modification can furnish new bioactive compounds. Biotransformation of 1 by fungus Syncephalastrum racemosum provided three derivatives, two hydroxylated products (2-3) and one product of rearrangement (4). Products 3 and 4 have never been reported so far, to the best of our knowledge. Structure of 3 was formed after oxidation and rearrangement of compound 2. Compounds 1-4 were evaluated for inhibition of acetylcholinesterase, enzyme linked to the symptomatic control of Alzheimer's disease. All the compounds presented inhibitory activity higher than starting material 1, and product 3 presented IC50 = 0.06 µM, which is about six times higher than activity found for galanthamine (IC50 = 0.38 µM), the positive control used in this assay.

A New Acetylcholinesterase Inhibitor from Green Glycosylation of Trachyloban-19-oic Acid by Mucor plumbeus

ABSTRACT The in vitro metabolism of a widespread natural product, trachyloban-19-oic acid (1), by the fungal species Mucor plumbeus was studied in a sucrose-yeast liquid medium. Two products were isolated, and their structures were determined by spectroscopic means as 7β-hydroxytrachyloban-19-oic acid (5) and trachyloban-19-O-β-D-glucopyranosyl ester (6). To the best of our knowledge, compound 6 is herein reported by the first time in the literature. These compounds were assayed for acetylcholinesterase inhibition along with some related compounds. Compound 6 showed the highest acetylcholinesterase inhibitory activity at 10000 µg/mL among the tested compounds, a result (92.89%) comparable to the activity of the positive control, galanthamine (94.21%). Therefore, biotransformation of the natural product 1 by M. plumbeus produced a novel compound with potential as a new lead to develop anti-Alzheimer medicines.