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

Biotransformation of the anabolic steroid dianabol (1) by suspended-cell cultures of the filamentous fungi Cunninghamella elegans and IVIacrophomina 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 0,1 713-dihydroxy-1 7ct-methylandrost-1,4dien-3-one (2), 1 5 ct,1 70-dihydroxy-1 7ot-methylandrost-1,4-dien-3-one (3), 1 1 cx,1 7 p-dihydroxy-1 7amethylandrost- 1,4-dien-3-one (4), 613,120,1 7 p-trihydroxy-1 7a-methylandrost-1,4-dien-3 -one (5), 613,1 5 cc,1 70-trihydroxy-1 7ct-methylandrost-1,4-dien-3-one (6), 1713-hydroxy-1 7ct-methylandrost-1,4dien-3,6-dione (7), 713,1 70,-dihydroxy-1 7a-methylandros 1,4-dien-3-one (8), 1513,1 70-dihydroxy-1 7otmethylandrost-1,4-dien-3-one (9), 17 13-hydroxy-17a-methylandrost-1,4-dien-3,1 1 -dione (10), and 1 113,17p-dihydroxy-17a-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 (I). The structures of all transformed products were deduced on the basis of spectral analyses. Compounds 1-14 were evaluated for p-glucuronidase enzyme inhibitory activity. Compounds 7, 13, and 14 showed a strong inhibition of p-glucuronidase enzyme, with IC50 values between 49.0 and 84.9 [1.M. 0 2014 Elsevier Inc. All rights reserved.