11 research outputs found
Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone
<p>Abstract</p> <p>Background</p> <p>Biotransformation of organic compounds by using microbial whole cells provides an efficient approach to obtain novel analogues which are often difficult to synthesize chemically. In this manuscript, we report for the first time the microbial transformation of a synthetic anabolic steroidal drug, oxymetholone, by fungal cell cultures.</p> <p>Results</p> <p>Incubation of oxymetholone (<b>1</b>) with <it>Macrophomina phaseolina</it>, <it>Aspergillus niger</it>, <it>Rhizopus stolonifer</it>, and <it>Fusarium lini</it> produced 17β-hydroxy-2-(hydroxy-methyl)-17α-methyl-5α-androstan-1-en-3-one (<b>2</b>), 2α,17α-di(hydroxyl-methyl)-5α-androstan-3β,17β-diol (<b>3</b>), 17α-methyl-5α-androstan-2α,3β,17β-triol (<b>4</b>), 17β-hydroxy-2-(hydroxymethyl)-17α-methyl-androst-1,4-dien-3-one (<b>5</b>), 17β-hydroxy-2α-(hydroxy-methyl)-17α-methyl-5α-androstan-3-one (<b>6</b>), and 2α-(hydroxymethyl)-17α-methyl-5α-androstan-3β-17β-diol (<b>7</b>). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds <b>2</b>–<b>5</b> were identified as the new metabolites of <b>1</b>. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds <b>1</b>–<b>7</b> were evaluated by observing their effects on T-cell proliferation, reactive oxygen species (ROS) production, and normal cell growth in MTT assays, respectively. These compounds showed immunosuppressant effect in the T-cell proliferation assay with IC<sub>50</sub> values between 31.2 to 2.7 μg/mL, while the IC<sub>50</sub> values for ROS inhibition, representing anti-inflammatory effect, were in the range of 25.6 to 2.0 μg/mL. All the compounds were found to be non-toxic in a cell-based cytotoxicity assay.</p> <p>Conclusion</p> <p>Microbial transformation of oxymetholone (<b>1</b>) provides an efficient method for structural transformation of <b>1</b>. The transformed products were obtained as a result of <it>de novo</it> stereoselective reduction of the enone system, isomerization of double bond, insertion of double bond and hydroxylation. The transformed products, which showed significant immunosuppressant and anti-inflammatory activities, can be further studied for their potential as novel drugs.</p
Inability of oxymetholone to elicit an erythropoietin-hypersecretory state in orchidectomised male mice
Comparison of 1 mg and 2 mg Overnight Dexamethasone Suppression Tests for the Screening of Cushing's Syndrome in Obese Patients
Management control systems (MCS) change and the impact of top management characteristics: the case of healthcare organisations
Cushing’s disease, pseudo-Cushing states and the dexamethasone test: a historical and critical review
Risk for opportunistic disease and death after reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy: a randomized trial.
Collaboratore per la suddetta ricerca multicentrica in quanto membro di SMART Study Grou
Interruption of antiretroviral therapy is associated with increased plasma cystatin C.
Collaboratore della suddetta ricerca in quanto membro del INSIGHT SMART Study Grou
Viral resuppression and detection of drug resistance following interruption of a suppressive non-nucleoside reverse transcriptase inhibitor-based regimen.
Collaboratore per la suddetta ricerca multicentrica in quanto membro di SMART Study Group