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Page 46 of 50 Siddiqui et al. Chem Synth 2023;3:25 https://dx.doi.org/10.20517/cs.2023.02

Biotransformed products, 17β-hydroxy-1-methyl-5α-androst-1-ene-3, 16-dione (236), and 15β, 17β -
dihydroxy-1-methyl-5α-androstan-1-ene-3-one (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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Derivative, 14β, 17β-dihydroxy-2-(hydroxymethyl)-17α-pregn-4-en-20-yn-3-one (241) showed potent
cytotoxicity against HeLa cancer cell line with the IC = 0.283 ± 0.013 μM, as compared to the standard
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drug, doxorubicin (IC = 0.506 ± 0.015 μM). Metabolite, 11α-hydroxy-6-methylene-androsta-1, 4-diene-3,
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17-dione (319) showed moderate cytotoxicity against PC-3 (IC = 16.83 ± 0.96 μM) and cancer HeLa (IC =
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24.87 ± 0.72 μM). Metabolite 2α-methyl-5α-androsta-17β-hydroxy-3-one (342) (IC = 19.6 ± 1.4 µM)
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exhibited potent activity against HeLa cells, in contrast to drostanolone enanthate (334) (IC = 54.7 ± 1.6 µ
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M), and standard cisplatin (IC = 40.1 ± 2.0 µM). Derivatives, 2α-methyl-3α, 14α, 17β-trihydroxy-5α-
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androstane (335) (IC = 64.3 ± 3.0 µM), 2-methylandrosta-11α-hydroxy-1, 4-diene-3, 17-dione (336) (IC =
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40.7 ± 0.9 µM), 2-methylandrosta-14α-hydroxy-1, 4-diene-3, 17-dione (337) (IC = 40.7 ± 0.9 µM), 2α-
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methyl-3α,17β-dihydroxy-5α-androstane (338) (IC = 49.5 ± 2.2 µM), 2-methylandrosta-1, 4-diene-3, 17-
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dione (339) (IC = 39.8 ± 1.5 µM), 2-methyl-5α-androsta-7α-hydroxy-1-ene-3, 17-dione (341) (IC = 58.0 ±
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1.0 µM), and 2α-methyl-5α-androsta-17β-hydroxy-3-one (342) (IC = 30.1 ± 1.0 µM) also displayed a
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remarkable activity against HeLa cell line. Metabolites 335 (IC = 58.4 ± 1.6 µM), 336 (IC = 59.1 ± 2.6 µM),
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337 (IC = 60.4 ± 0.9 µM), 338 (IC = 51.8 ± 3.4 µM), 339 (IC = 68.1 ± 1.2 µM), and 340 (IC = 39.1 ± 2.0 µ
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M) showed significant anti-cancer activity against PC-3 cells, compared to compounds 342 (IC = 96.2 ± 3.0
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µM), 335 (IC = 84.6 ± 6.4 µM), 339 (IC = 84.0 ± 3.1 µM), and standard cisplatin (IC = 76.5 ± 1.2 µM).
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Compounds 334 (IC = 5.0 ± 1.2 µM), 338 (IC = 12.4 ± 2.3 µM), 340 (IC = 16.7 ± 2.6 µM), and 90 (IC =
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14.7 ± 2.6 µM) showed potent activity against H460 cells, as compared to cisplatin (IC = 22.2 ± 2.1 µM).
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Compounds 335 (IC = 44.4 ± 2.0 µM), 336 (IC = 33.2 ± 1.0 µM), 337 (IC = 38.5 ± 2.8 µM), 339 (IC =
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31.9 ± 1.8 µM), and 340 (IC = 26.4 ± 0.9 µM) also presented good anti-cancer activity against H460 cells.
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Compound 334 (IC = 3.1 ± 3.2 µM) showed potent anti-cancer activity against HCT116 cells, in contrast to
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standard cisplatin (IC = 11.2 ± 3.0 µM).
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Physalin H (373) (IC = 6.03 ± 0.005 μM), and its structural analogues, 6, 7-dehydrophysalin H (374) (IC =
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7.74 ± 0.015 μM), 6-deoxyphysalin H (375) (IC = 6.34 ± 0.03 μM), and isophysalin B (376) (IC = 13.8 ±
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0.05 μM), showed potent anti-leishmanial activity, compared to the standard drug, amphotericin B (IC =
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0.129 ± 0.105 μM), against promastigotes of Leishmania major (DESTO).
CONCLUSION AND FUTURE PERSPECTIVES
The scope of present biotransformation studies conducted in our laboratories was to synthesize new
analogues of monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, and steroidal-based
anabolic, contraceptive, anti-cancer, and anti-epileptic drugs by using the cost-effective, and eco-friendly
bio-catalytic approach. In the present review, over 350 new and known metabolites are presented through
biotransformation of natural/synthetic/semisynthetic compounds. Aromatization, hydroxylation,
epoxidation, hydrogenation, and dehydrogenation were the main reactions that occurred during the whole-
cell bio-catalyzed transformation reactions. The technique of biotransformation was found to be a robust
method to produce compounds having structural similarities with their parent molecules. Newly
synthesized derivatives were evaluated for various biological activities. Variations in the structures of the
transformed products often led to changes in their biological activities in comparison to their parent drugs.
Several bio-transformed products exhibit biological activities and have been explored for different
applications, mainly in the food and pharmaceutical industries. These structurally altered compounds are
extensively being studied for their effects on human health. In the search for biologically active compounds,