Bio-Catalytic Structural Transformation of Anti-cancer Steroid, Drostanolone Enanthate with and , and Cytotoxic Potential Evaluation of Its Metabolites against Certain Cancer Cell Lines.

In search of selective and effective anti-cancer agents, eight metabolites of anti-cancer steroid, drostanolone enanthate (), were synthesized microbial biotransformation. Enzymes such as reductase, oxidase, dehydrogenase, and hydrolase from , and were likely involved in the biotransformation of into new metabolites at pH 7.0 and 26°C, yielding five new metabolites, 2α-methyl-3α,14α,17β-trihydroxy-5α-androstane (), 2α-methyl-7α-hydroxy-5α-androstan-3,17-dione (), 2-methylandrosta-11α-hydroxy-1, 4-diene-3,17-dione (), 2-methylandrosta-14α-hydroxy-1,4-diene-3,17-dione (), and 2-methyl-5α-androsta-7α-hydroxy-1-ene-3,17-dione (), along with three known metabolites, 2α-methyl-3α,17β-dihydroxy-5α-androstane (), 2-methylandrosta-1, 4-diene-3,17-dione (), and 2α-methyl-5α-androsta-17β-hydroxy-3-one (), on the basis of NMR, and HREI-MS data, and single-crystal X-ray diffraction techniques. Interestingly, and were able to catalyze hydroxylation only at alpha positions of . Compounds showed a varying degree of cytotoxicity against HeLa (human cervical carcinoma), PC3 (human prostate carcinoma), H460 (human lung cancer), and HCT116 (human colon cancer) cancer cell lines. Interestingly, metabolites (IC = 49.5 ± 2.2 μM), (IC = 39.8 ± 1.5 μM), (IC = 40.7 ± 0.9 μM), (IC = 43.9 ± 2.4 μM), (IC = 19.6 ± 1.4 μM), and (IC = 25.1 ± 1.6 μM) were found to be more active against HeLa cancer cell line than the substrate (IC = 54.7 ± 1.6 μM). Similarly, metabolites (IC = 84.6 ± 6.4 μM), (IC = 68.1 ± 1.2 μM), (IC = 60.4 ± 0.9 μM), (IC = 84.0 ± 3.1 μM), (IC = 58.4 ± 1.6 μM), (IC = 59.1 ± 2.6 μM), (IC = 51.8 ± 3.4 μM), and (IC = 57.8 ± 3.2 μM) were identified as more active against PC-3 cancer cell line than the substrate (IC = 96.2 ± 3.0 μM). Metabolite (IC = 2.8 ± 0.2 μM) also showed potent anticancer activity against HCT116 cancer cell line than the substrate (IC = 3.1 ± 3.2 μM). In addition, compounds showed no cytotoxicity against 3T3 normal cell line, while compounds (IC = 74.6 ± 3.7 μM), and (IC = 62.1 ± 1.2 μM) were found to be weakly cytotoxic.