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Page 22 of 50 Siddiqui et al. Chem Synth 2023;3:25 https://dx.doi.org/10.20517/cs.2023.02

Figure 37. Microbial transformation of nandrolone (175) with Cunninghamella blakesleeana, Cunninghamella echinulata, and Rhizopus
stolonifer.

Biotransformation of oxandrolone (184)
Rhizopus stolonifer-assisted transformation of the steroidal lactone, oxandrolone (184) yielded three new
metabolites, 11α,17β-dihydroxy-2-oxa-androstan-3-one (185) (25%), 6α, 17β-dihydroxy-2-oxa-androstan-3-
one (186) (5.0%), and 9α, 17β-dihydroxy-2-oxa-androstan-3-one (187) (8.0%) [Figure 38]. Compounds 185
(IC = 190.3 ± 1.18 μM) and 187 (IC = 482.66 ± 6.86 μM) showed weak inhibition of β-glucuronidase, as
50
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compared to the standard inhibitor, D-saccharic acid 1, 4 lactone (IC = 48.4 ± 1.25 μM) .
[58]
50
A new metabolite, 12β,17β-dihydroxy-17α-methyl-2-oxa-5α-androstan-3-one (188) (3.4%), was synthesized
via the transformation of substrate 184 with Cunninghamella blakesleeana [Figure 38]. Similarly,
[59]
structural transformation of oxandrolone (184) with Macrophomina phaseolina afforded four new
metabolites, 11β, 17β-dihydroxy-17α-(hydroxymethyl)-2-oxa-5α-androstan-3-one (189) (2.5%), 5α, 11β, 17β-
trihydroxy-17α-methyl-2-oxa-androstan-3-one (190) (1.0%), 17β-hydroxy-17α-methyl-2-oxa-5α-androstan-
3, 11-dione (191) (1.5%), and 11β, 17β-dihydroxy-17α-methyl-2-oxa-5α-androstan-3-one (192) (3.0%)
[59]
[Figure 38]. Glomerella fusarioides-mediated transformation of oxandrolone (184) also yielded a new
compound, 17β, 11α-dihydroxy-17α-methylandrosta-2-oxa-4-ene-3-one (193) (3.8%) [Figure 38]. The
[60]
new metabolite 193 showed a remarkable aromatase inhibitory activity with an IC = 0.6 ± 0.005 µM, as
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compared to the substrate 184 (IC = 0.808 ± 0.07 µM), and standard anti-breast cancer drug exemestane
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(IC = 0.232 ± 0.031 µM) . Aromatase is an enzyme that catalyzes the production of estrogen through the
[60]
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aromatization of steroidal ring-A, and thus helps in the proliferation of breast cancer cells. Its inhibition is
the standard treatment of ER+ breast cancers.
Biotransformation of mesterolone (194)
Mesterolone (194) is a steroidal anabolic-androgenic drug used for the treatment of disorders in men where
their bodies cannot produce enough natural androgens. Eight metabolites, 1α-methylandrostane-3, 17-dione
(195) (1.2%), 1-methylandrost-1-en-3, 17-dione (196) (0.25%), 6α, 17β-dihydroxy-1α-methylandrosta-3-one
(197) (0.36%), 7α, 17β-dihydroxy-1α-methylandrosta-3-one (198) (0.60%), 11α, 17β-dihydroxy-1α-
methylandrosta-3-one (199) (0.55%), 15α-hydroxy-1α-methylandrosta-3, 17-dione (200) (1.05%), 15α, 17β-
dihydroxy-1α-methylandrosta-3-one (201) (0.86%), 15α, 17β-dihydroxy-1-methylandrosta-1en-3-one (202)
(0.37%), and 3β, 17β-dihydroxy-1α-methylandrostane (203) (0.65%) of mesterolone (194) were synthesized
by using Cephalosporium aphidicola, Fusarium lini, and Rhizopus stolonifer fungal cell cultures. Metabolites