Biotransformation of dianabol with the filamentous fungi and ß-glucuronidase inhibitory activity of resulting metabolites.

Biotransformation of the anabolic steroid dianabol (1) by suspended-cell cultures of the filamentous fungi Cunninghamella elegans and Macrophomina phaseolina was studied. Incubation of 1 with C. elegans yielded five hydroxylated metabolites 2-6, while M. phaseolina transformed compound 1 into polar metabolites 7-11. These metabolites were identified as 6ß,17ß-dihydroxy-17α-methylandrost-1,4-dien-3-one (2), 15α,17ß-dihydroxy-17α-methylandrost-1,4-dien-3-one (3), 11α,17ß-dihydroxy-17α-methylandrost-1,4-dien-3-one (4), 6ß,12ß,17ß-trihydroxy-17α-methylandrost-1,4-dien-3-one (5), 6ß,15α,17ß-trihydroxy-17α-methylandrost-1,4-dien-3-one (6), 17ß-hydroxy-17α-methylandrost-1,4-dien-3,6-dione (7), 7ß,17ß,-dihydroxy-17α-methylandrost-1,4-dien-3-one (8), 15ß,17ß-dihydroxy-17α-methylandrost-1,4-dien-3-one (9), 17ß-hydroxy-17α-methylandrost-1,4-dien-3,11-dione (10), and 11ß,17ß-dihydroxy-17α-methylandrost-1,4-dien-3-one (11). Metabolite 3 was also transformed chemically into diketone 12 and oximes 13, and 14. Compounds 6 and 12-14 were identified as new derivatives of dianabol (1). The structures of all transformed products were deduced on the basis of spectral analyses. Compounds 1-14 were evaluated for ß-glucuronidase enzyme inhibitory activity. Compounds 7, 13, and 14 showed a strong inhibition of ß-glucuronidase enzyme, with IC50 values between 49.0 and 84.9 µM.

Biotransformation of adrenosterone by filamentous fungus, Cunninghamella elegans.

Microbial transformation of adrenosterone (1) by suspended-cell cultures of the filamentous fungus Cunninghamella elegans resulted in the production of five metabolites 2-6, which were identified as 9alpha-hydroxyadrenosterone (2), 11-ketotestosterone (3), 6beta-hydroxyadrenosterone (4), 9alpha-hydroxy-11-ketotestosterone (5), and 6beta-hydroxy-11-ketotestosterone (6). Structures of new metabolites 2, 5, and 6 were established by single-crystal X-ray diffraction analysis.