Biocatalytic transformation of steroidal drugs oxandrolone and ganaxolone, and aromatase inhibitory activity of transformed products.

[Display omitted] • New metabolite 2 of oxandrolone (1) was obtained through biotransformation. • New metabolite 4 of ganaxolone (3) was synthesized through biotransformation. • Derivative 2 showed a potent anti-aromatase activity (IC 50 = 0.6 ± 0.005 μM). • Ganaxolone (1) showed a good aromatase inhibitory activity (IC 50 = 13.76 ± 2.00 μM). • Compounds 1 - 4 were found to be non-cytotoxic to 3T3 cell line. Glomerella fusarioides- mediated structural modifications of steroidal anabolic drug, oxandrolone (1), yielded a new product 17 β ,11 α -dihydroxy-17 α -methylandrosta-2-oxa-4-ene-3-one (2). Similarly, Cunninghamella elegans -catalyzed transformation of a steroidal anti-epileptic drug ganaxolone (3) afforded a new metabolite 14 α -hydroxy-5 α -pregnan-1-ene-3,20-dione (4). Structures of new metabolites 2 and 4 were deduced via 1D-, and 2D-NMR, HREI-, HRFAB-MS, and IR spectroscopic techniques. New derivative 2 showed a remarkable anti-aromatase activity with an IC 50 = 0.6 ± 0.005 μM, when compared to substrate 1 (IC 50 = 0.808 ± 0.07 μM), and standard anti-cancer drug exemestane (IC 50 = 0.232 ± 0.031 μM). Ganaxolone (3) (IC 50 = 13.76 ± 2.00 μM) also showed a good activity against human aromatase enzyme, while its derivative 4 was found to be inactive. Inhibition of aromatase enzyme is a key approach in the treatment of estrogen positive breast cancers. Compounds 1 - 4 were non-cytotoxic to 3T3 cell line (mouse fibroblast). [ABSTRACT FROM AUTHOR]