Biotransformation of 11-ketoprogesterone by Filamentous Fungus, &lt;i&gt;Fusarium lini&lt;/i&gt;

Al-Maruf, M. A.; Khan, Niaz Ali; Saki, Mojgan; Choudhary, Muhammad Iqbal; Ali, Md. Hasan; Jahirul, M.I.

doi:10.3329/jsr.v3i2.6221

Cited by 3 publications

(1 citation statement)

References 14 publications

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“…M. phaseolina is previously reported to catalyze the introduction of double bond between C-1 and C-2, hydroxyl groups at C-6, C-15, C-16 and C-17, and carbonyl group at C-17 of the steroidal skeleton [1,20]. F. lini is also reported to catalyze the oxidation at C-1, C-2, C-6, and C-11 of steroidal skeleton [21]. The chemical structures of the metabolites 2 - 4 are reported here for the first time along with their NMR data (Tables 1 and 2).…”

Section: Resultsmentioning

confidence: 99%

Microbial transformation of anti-cancer steroid exemestane and cytotoxicity of its metabolites against cancer cell lines

Baydoun

Bibi

Iqbal

et al. 2013

Chemistry Central Journal

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BackgroundMicrobial transformation of steroids has been extensively used for the synthesis of steroidal drugs, that often yield novel analogues, not easy to obtain by chemical synthesis. We report here fungal transformation of a synthetic steroidal drug, exemestane, used for the treatment of breast cancer and function through inhibition of aromatase enzyme.ResultsMicrobial transformation of anti-cancer steroid, exemestane (1), was investigated by using two filamentous fungi. Incubation of 1 with fungi Macrophomina phaseolina, and Fusarium lini afforded three new, 11α-hydroxy-6-methylene-androsta-1, 4-diene-3,17-dione (2), 16β, 17β-dihydroxy-6-methylene-androsta-1, 4-diene-3-one (3), and 17β-hydroxy-6-methylene-androsta-1, 4-diene-3, 16-dione (4), and one known metabolites, 17β-hydroxy-6-methylene-androsta-1, 4-diene-3-one (5). Their structures were deduced spectroscopically. Compared to 1 (steroidal aromatase inactivator), the transformed metabolites were also evaluated for cytotoxic activity by using a cell viability assay against cancer cell lines (HeLa and PC3). Metabolite 2 was found to be moderately active against both the cell lines.ConclusionsBiotransformation of exemestane (1) provides an efficient method for the synthesis of new analogues of 1. The metabolites were obtained as a result of reduction of double bond and hydroxylation. The transformed product 2 exhibited a moderate activity against cancer cell lines (HeLa and PC3). These transformed products can be studied for their potential as drug candidates.

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Section: Resultsmentioning

confidence: 99%

Microbial transformation of anti-cancer steroid exemestane and cytotoxicity of its metabolites against cancer cell lines

Baydoun

Bibi

Iqbal

et al. 2013

Chemistry Central Journal

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New Anti-Inflammatory Metabolites by Microbial Transformation of Medrysone

et al. 2016

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Microbial transformation of the anti-inflammatory steroid medrysone (1) was carried out for the first time with the filamentous fungi Cunninghamella blakesleeana (ATCC 8688a), Neurospora crassa (ATCC 18419), and Rhizopus stolonifer (TSY 0471). The objective was to evaluate the anti-inflammatory potential of the substrate (1) and its metabolites. This yielded seven new metabolites, 14α-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (2), 6β-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (3), 15β-hydroxy-6α-methylpregn-4-ene-3,11,20-trione (4), 6β,17α-dihydroxy-6α-methylpregn-4-ene-3,11,20-trione (5), 6β,20S-dihydroxy-6α-methylpregn-4-ene-3,11-dione (6), 11β,16β-dihydroxy-6α-methylpregn-4-ene-3,11-dione (7), and 15β,20R-dihydroxy-6α-methylpregn-4-ene-3,11-dione (8). Single-crystal X-ray diffraction technique unambiguously established the structures of the metabolites 2, 4, 6, and 8. Fungal transformation of 1 yielded oxidation at the C-6β, -11β, -14α, -15β, -16β positions. Various cellular anti-inflammatory assays, including inhibition of phagocyte oxidative burst, T-cell proliferation, and cytokine were performed. Among all the tested compounds, metabolite 6 (IC50 = 30.3 μg/mL) moderately inhibited the reactive oxygen species (ROS) produced from zymosan-induced human whole blood cells. Compounds 1, 4, 5, 7, and 8 strongly inhibited the proliferation of T-cells with IC50 values between <0.2–10.4 μg/mL. Compound 7 was found to be the most potent inhibitor (IC50 < 0.2 μg/mL), whereas compounds 2, 3, and 6 showed moderate levels of inhibition (IC50 = 14.6–20.0 μg/mL). Compounds 1, and 7 also inhibited the production of pro-inflammatory cytokine TNF-α. All these compounds were found to be non-toxic to 3T3 cells (mouse fibroblast), and also showed no activity when tested against HeLa (human epithelial carcinoma), or against PC3 (prostate cancer) cancer cell lines.

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Fungal Biotransformation: An Efficient Approach for Stereoselective Chemical Reactions

Santos

Neto

Júnior

et al. 2020

COC

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Abstract:: There is great interest in developing chemical technologies to achieve regioselective and stereoselective reactions since only one enantiomer is required for producing the chiral leads for drug development. These selective reactions are dif-ficultly provided by traditional chemical synthetic methods, even under expensive catalysts and long reaction times. Fila-mentous fungi are efficient biocatalysts capable of catalyzing a wide variety of reactions with significant contributions to the development of clean and selective processes. Although some enzymes have already been employed in isolated forms or as crude protein extracts as catalysts for conducting selective reactions, the use of whole-cell provides advantages regarding cofactor regenerations. It is also possible to carry out conversions at chemically unreactive positions and to perform racemic resolution through microbial transformation. The current literature contains several reports on the biotransformation of dif-ferent compounds by fungi, which generated chemical analogs with high selectivity, using mild and eco-friendly conditions. Prompted by the enormous pharmacological interest in the development of stereoselective chemical technologies, this re-view covers the biotransformations catalyzed by fungi that yielded chiral products with enantiomeric excesses published over the period 2010-2020. This work highlights new approaches for the achievement of a variety of bioactive chiral build-ing blocks, which can be a good starting point for the synthesis of new compounds combining biotransformation and syn-thetic organic chemistry.

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Biotransformation of 11-ketoprogesterone by Filamentous Fungus, <i>Fusarium lini</i>

Cited by 3 publications

References 14 publications

Microbial transformation of anti-cancer steroid exemestane and cytotoxicity of its metabolites against cancer cell lines

Microbial transformation of anti-cancer steroid exemestane and cytotoxicity of its metabolites against cancer cell lines

New Anti-Inflammatory Metabolites by Microbial Transformation of Medrysone

Fungal Biotransformation: An Efficient Approach for Stereoselective Chemical Reactions

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