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Page 26 of 50 Siddiqui et al. Chem Synth 2023;3:25 https://dx.doi.org/10.20517/cs.2023.02

3.3%), and 233 (71.0% ± 7.2%) showed good inhibition of cytokine (TNF-α) production. Compounds 223
(53.7% ± 1.4 %), 226 (46.6% ± 5.2 %), and 234 (52.9% ± 2.4%) showed moderate activity, compounds 222
(33.5% ± 6.6%), and 225 (37.8% ± 1.1%) showed a weak activity, while metabolites 228, 234, and 235 were
found inactive. Compounds 222 (IC = 4.4 ± 0.01 µg/mL), and 224 (IC = 10.2 ± 0.01 µg/mL) showed
50
50
significant activity against T-cells proliferation, in contrast to the standard drug, prednisolone (IC = 3.51 ±
50
0.03 µg/mL) in vitro . TNF- α, and T-cells are essential components of innate inflammatory cascade, and
[65]
their inhibition is used for the treatment of chronic inflammations.
Biotransformation of metenolone enanthate (235)
Four new derivatives of steroidal anabolic drug, metenolone enanthate (235), namely 17β-hydroxy-1-
methyl-5α-androst-1-ene-3, 16-dione (236), 15β, 17β -dihydroxy-1-methyl-5α-androstan-1-ene-3-one (237),
12β, 17β -dihydroxy-1-methyl-5α-androstan-1-ene-3-one (238), and 16β, 17β-dihydroxy-1-methyl-5α-
androstan-1-ene-3-one (239), were obtained through biotransformation of drug 235 with Aspergillus niger
[66]
[Figure 44]. The metabolites 236 and 237 showed potent inhibition of ROS production by whole blood with
the IC values of 8.60 ± 1.0 and 7.05 ± 1.3 μg/mL, respectively, while drug 235 was found to be inactive.
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Compounds 236 and 237 also showed potent activity against isolated polymorphonuclear leukocytes
(PMNs) with the IC values of 14.0 ± 1.7 and 4.70 ± 0.5 μg/mL, respectively.
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Biotransformation of danazol (240)
Cunninghamella blakesleeana-catalyzed transformation of the anabolic steroidal drug, danazol (240),
afforded three new metabolites, 15β, 17β-dihydroxy-2-(hydroxymethyl)-17α-pregn-4-en-20-yn-3-one (241)
(1.0%), 1α, 17β-dihydroxy-17α-pregna-2, 4-dien-20-yno-[2, 3-d]-isoxazole (242) (1.2%), 6β, 17β-dihydroxy-
17α-pregna-2, 4-dien-20-yno-[2,3-d]-isoxazole (243) (0.8%), along with the known metabolite, 17β-
hydroxy-2-(hydroxymethyl)-17α-pregn-1, 4-dien-20-yn-3-one (244) (1.2%) [Figure 45]. Compound 241
[67]
showed potent cytotoxicity against HeLa (cervical) cancer cell line with the IC = 0.283 ± 0.013 μM, as
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compared to the standard anti-cancer drug, doxorubicin (IC = 0.506 ± 0.015 μM), where compound 242
50
[67]
was identified as significantly active (IC = 13.42 ± 0.819 μM) .
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Biotransformation of dianabol (245)
Biotransformation of another anabolic steroidal drug dianabol (245) with Cunninghamella elegans afforded
five new metabolites, 6β, 17β-dihydroxy-17α-methylandrost-1, 4-dien-3-one (246) (3.7%), 15α, 17β-
dihydroxy-17α-methylandrost-1, 4-dien-3-one (247) (18.6%), 11α, 17β-dihydroxy-17α-methylandrost-1, 4-
dien-3-one (248) (13.0%), 6β, 12β, 17β-trihydroxy-17α-methylandrost-1, 4-dien-3-one (249) (4.0%), 6β, 15α,
17β-trihydroxy-17α-methylandrost-1, 4-dien-3-one (250) (3.2%) [Figure 46]. Three new metabolites, 17β-
[68]
hydroxy-17α-methylandrost-1,4-dien-3,6-dione (251) (1.2%), 7β, 17β-dihydroxy-17α-methylandrost-1, 4-
dien-3-one (252) (11.0%), and 15β, 17β-dihydroxy-17α-methylandrost-1, 4-dien-3-one (253) (3.0%), along
with the known metabolite, 11β, 17β-dihydroxy-17α-methylandrost-1, 4-dien-3-one (254) (1.7%) were
synthesized by Macrophomina phaseolina-assisted biotransformation of drug 245. The metabolite 247
showed a remarkable β-glucuronidase inhibitory activity (IC = 60.7 μM), as compared to the standard, D-
50
[68]
saccharic acid-1, 4-lactone (IC = 48.4 μM) .
50
Biotransformation of methasterone (255)
Five new derivatives, 7α, 17β-dihydroxy-2α, 17α-dimethyl-5α-androstane-3-one (256) (2.0%), 7α, 16β, 17β-
triihydroxy-2α, 17α-dimethyl-5α-androstane-3-one (257) (0.7%), 5α, 12β, 17β-trihydroxy-2α, 17α-dimethyl-5
α-androstane-3-one (258) (1.0%), 7α, 12β, 17β-triihydroxy-2α, 17α-dimethyl-5α-androstane-3-one (259)
(1.5%), and 7α, 9α, 17β-triihydroxy-2α, 17α-dimethyl-5α-androstane-3-one (260) (0.5%) were isolated
through biotransformation of steroidal anabolic drug, methasterone (255) with Cunninghamella
blakesleeana. Likewise, six new derivatives, 6β, 17β-dihydroxy-2, 17α-dimethylandrosta-1, 4, 14-triene-3-one