Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone

Naik Tameen Khan, Marium Bibi, Sammer Yousuf, Izhar Husain Qureshi, Atta-ur-Rahman, Abdullah Mohammad Al-Majid, Osman Mesaik Mohammed Ahmed Hassan, Ahmed Shukralla Khalid, Samina A. Sattar, Atia-tul-Wahab, M. Iqbal Choudhary

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: 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.Results: Incubation of oxymetholone (1) with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17β-hydroxy-2-(hydroxy-methyl)-17α-methyl-5α-androstan-1-en-3-one (2), 2α,17α-di(hydroxyl-methyl)-5α-androstan-3β,17β-diol (3), 17α-methyl-5α-androstan-2α,3β,17β-triol (4), 17β-hydroxy-2-(hydroxymethyl)-17α-methyl-androst-1,4-dien-3-one (5), 17β-hydroxy-2α-(hydroxy-methyl)-17α-methyl-5α-androstan-3-one (6), and 2α-(hydroxymethyl)-17α-methyl-5α-androstan-3β-17β-diol (7). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2-5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1-7 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 IC50 values between 31.2 to 2.7 μg/mL, while the IC50 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.Conclusion: Microbial transformation of oxymetholone (1) provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo 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.

Original languageEnglish
Article number153
JournalChemistry Central Journal
Volume6
Issue number1
DOIs
Publication statusPublished - 10 Dec 2012
Externally publishedYes

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Oxymetholone
Testosterone Congeners
Metabolites
Assays
Anti-Inflammatory Agents
T-cells
Cell proliferation
Immunosuppressive Agents
Cytotoxicity
Reactive Oxygen Species
Hydroxylation
Aspergillus
Cell growth
Isomerization
Organic compounds
Cell culture
Pharmaceutical Preparations
Hydroxyl Radical
Single crystals
X ray diffraction

Keywords

  • 3T3 Fibroblast cells
  • Anabolic steroid
  • Anti-inflammation
  • Biotransformation
  • de novo Hydroxylation
  • Immunomodulation
  • Inhibition of reactive oxygen species production
  • Oxymetholone
  • T-Cell proliferation inhibition

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone. / Khan, Naik Tameen; Bibi, Marium; Yousuf, Sammer; Qureshi, Izhar Husain; Atta-ur-Rahman; Al-Majid, Abdullah Mohammad; Mohammed Ahmed Hassan, Osman Mesaik; Khalid, Ahmed Shukralla; Sattar, Samina A.; Atia-tul-Wahab; Choudhary, M. Iqbal.

In: Chemistry Central Journal, Vol. 6, No. 1, 153, 10.12.2012.

Research output: Contribution to journalArticle

Khan, NT, Bibi, M, Yousuf, S, Qureshi, IH, Atta-ur-Rahman, Al-Majid, AM, Mohammed Ahmed Hassan, OM, Khalid, AS, Sattar, SA, Atia-tul-Wahab & Choudhary, MI 2012, 'Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone', Chemistry Central Journal, vol. 6, no. 1, 153. https://doi.org/10.1186/1752-153X-6-153
Khan, Naik Tameen ; Bibi, Marium ; Yousuf, Sammer ; Qureshi, Izhar Husain ; Atta-ur-Rahman ; Al-Majid, Abdullah Mohammad ; Mohammed Ahmed Hassan, Osman Mesaik ; Khalid, Ahmed Shukralla ; Sattar, Samina A. ; Atia-tul-Wahab ; Choudhary, M. Iqbal. / Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone. In: Chemistry Central Journal. 2012 ; Vol. 6, No. 1.
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abstract = "Background: 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.Results: Incubation of oxymetholone (1) with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17β-hydroxy-2-(hydroxy-methyl)-17α-methyl-5α-androstan-1-en-3-one (2), 2α,17α-di(hydroxyl-methyl)-5α-androstan-3β,17β-diol (3), 17α-methyl-5α-androstan-2α,3β,17β-triol (4), 17β-hydroxy-2-(hydroxymethyl)-17α-methyl-androst-1,4-dien-3-one (5), 17β-hydroxy-2α-(hydroxy-methyl)-17α-methyl-5α-androstan-3-one (6), and 2α-(hydroxymethyl)-17α-methyl-5α-androstan-3β-17β-diol (7). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2-5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1-7 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 IC50 values between 31.2 to 2.7 μg/mL, while the IC50 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.Conclusion: Microbial transformation of oxymetholone (1) provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo 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.",
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T1 - Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone

AU - Khan, Naik Tameen

AU - Bibi, Marium

AU - Yousuf, Sammer

AU - Qureshi, Izhar Husain

AU - Atta-ur-Rahman,

AU - Al-Majid, Abdullah Mohammad

AU - Mohammed Ahmed Hassan, Osman Mesaik

AU - Khalid, Ahmed Shukralla

AU - Sattar, Samina A.

AU - Atia-tul-Wahab,

AU - Choudhary, M. Iqbal

PY - 2012/12/10

Y1 - 2012/12/10

N2 - Background: 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.Results: Incubation of oxymetholone (1) with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17β-hydroxy-2-(hydroxy-methyl)-17α-methyl-5α-androstan-1-en-3-one (2), 2α,17α-di(hydroxyl-methyl)-5α-androstan-3β,17β-diol (3), 17α-methyl-5α-androstan-2α,3β,17β-triol (4), 17β-hydroxy-2-(hydroxymethyl)-17α-methyl-androst-1,4-dien-3-one (5), 17β-hydroxy-2α-(hydroxy-methyl)-17α-methyl-5α-androstan-3-one (6), and 2α-(hydroxymethyl)-17α-methyl-5α-androstan-3β-17β-diol (7). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2-5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1-7 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 IC50 values between 31.2 to 2.7 μg/mL, while the IC50 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.Conclusion: Microbial transformation of oxymetholone (1) provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo 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.

AB - Background: 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.Results: Incubation of oxymetholone (1) with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17β-hydroxy-2-(hydroxy-methyl)-17α-methyl-5α-androstan-1-en-3-one (2), 2α,17α-di(hydroxyl-methyl)-5α-androstan-3β,17β-diol (3), 17α-methyl-5α-androstan-2α,3β,17β-triol (4), 17β-hydroxy-2-(hydroxymethyl)-17α-methyl-androst-1,4-dien-3-one (5), 17β-hydroxy-2α-(hydroxy-methyl)-17α-methyl-5α-androstan-3-one (6), and 2α-(hydroxymethyl)-17α-methyl-5α-androstan-3β-17β-diol (7). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2-5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1-7 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 IC50 values between 31.2 to 2.7 μg/mL, while the IC50 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.Conclusion: Microbial transformation of oxymetholone (1) provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo 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.

KW - 3T3 Fibroblast cells

KW - Anabolic steroid

KW - Anti-inflammation

KW - Biotransformation

KW - de novo Hydroxylation

KW - Immunomodulation

KW - Inhibition of reactive oxygen species production

KW - Oxymetholone

KW - T-Cell proliferation inhibition

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