Biotransformation of isoimperatorin and imperatorin by Glomerella cingulata and β-secretase inhibitory activity

Biotransformation studies conducted on the furanocoumarins isoimperatorin (1) and imperatorin (3) have revealed that 1 was metabolized by Glomerella cingulata to give the corresponding reduced acid, 6,7-furano-5-prenyloxy hydrocoumaric acid (2), and 3 was transformed by G. cingulata to give the dealkylated metabolite, xanthotoxol (4) in high yields (83% and 81%), respectively. The structures of the new compound 2 have been established on the basis of spectral data. The metabolites 2 and 4 were tested for the β-secretase (BACE1) inhibitory activity in vitro, and metabolite 2 slightly inhibited the β-secretase activity with an IC50 value of 185.6 ± 6.8 μM. The metabolite 4 was less potent activity than compounds 1–3. In addition, methyl ester (2Me), methyl ether (2a) and methyl ester and ether (2aMe) of 2 were synthesized, and investigated for the ability to inhibit β-secretase. Compound 2aMe exhibited the best β-secretase inhibitory activity at the IC50 value 16.2 ± 1.2 μM and found to be the 2aMe showed competitive mode of inhibition against β-secretase with Ki value 11.3 ± 2.8 μM.

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