Microbial transformation of cortisol and prolyl endopeptidase inhibitory activity of its transformed products

Incubation of cortisol (1) with Gibberella fujikuruoi for 12 days yielded an oxidatively cleaved product, 11β-hydroxyandrost-4-en-3,17-dione (2), while incubation with Bacillus subtilis and Rhizopus stolonifer yielded the reduced product, 11β, 17α,20,21-tetrahydroxy-(20S)-pregn-4-en-3-one (3). Other reduced products, 11β, 17α, 21-trihydroxy-5α-pregnan-3, 20-dione (4) and 3β, 11β, 17α, 21-tetrahydroxy-5α-pregnan-20-one (5) were obtained by incubation of compound 1 with Bacillus cerus. The inhibitory activity of compounds 1-5 against prolyl endopeptidase enzyme (PEP) was also assayed. Compounds 2 (IC50 162.8 μM) and 4 (IC50 157 μM) have shown significant inhibitory activity against PEP.