Fungal transformation and T-cell proliferation inhibitory activity of melengestrol acetate and its metabolite

Elias Baydoun, Saira Bano, Atia-Tul-Wahab, Almas Jabeen, Sammer Yousuf, Osman Mesaik Mohammed Ahmed Hassan, Colin Smith, M. Iqbal Choudhary

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Biotransformation of melengestrol acetate (MGA, 17α-acetoxy-6-methyl- 16-methylenepregna-4,6-diene-3,20-dione) (1) was investigated for the first time by using fungal cultures. Incubation of compound 1 with Cunninghamella blakesleeana yielded a new major metabolite, 17α-acetoxy-11β-hydroxy- 6-methyl-16-methylenepregna-4,6-diene-3,20-dione (2). The metabolite 2 was purified by using HPLC, followed by characterization through 1H- and 13C-NMR and other spectroscopic techniques. Single crystal X-ray diffraction analysis was used to deduce the three dimensional structures of melengestrol acetate (1) and metabolite 2 for the first time. T-cell proliferation assay was employed to evaluate the immunosuppressant effect of compounds 1 and 2 with IC50 = 0.5 ± 0.07 and 0.6 ± 0.08 μg/mL, respectively. The results indicated that these compounds possess sixfold potent T-cell proliferation inhibitory activity as compared to the standard prednisolone (IC50 <3.1 μg/mL). Both compounds were found to be non-toxic in a 3T3 (mouse fibroblast) cell-based cytotoxicity assay. This discovery of potent anti-inflammatory activity of compounds 1 and 2 can lead the way to develop new immunosuppressant compounds for clinical application.

Original languageEnglish
Pages (from-to)56-61
Number of pages6
JournalSteroids
Volume86
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Melengestrol Acetate
T-cells
Cell proliferation
Immunosuppressive Agents
Metabolites
Inhibitory Concentration 50
Cunninghamella
Cell Proliferation
T-Lymphocytes
Assays
Biotransformation
Prednisolone
X-Ray Diffraction
Anti-Inflammatory Agents
Fibroblasts
High Pressure Liquid Chromatography
Cytotoxicity
X ray diffraction analysis
Nuclear magnetic resonance
Single crystals

Keywords

  • Anti-inflammatory
  • Biotransformation
  • Cunninghamella blakesleeana
  • Melengestrol acetate

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Molecular Biology
  • Organic Chemistry
  • Pharmacology
  • Medicine(all)

Cite this

Fungal transformation and T-cell proliferation inhibitory activity of melengestrol acetate and its metabolite. / Baydoun, Elias; Bano, Saira; Atia-Tul-Wahab; Jabeen, Almas; Yousuf, Sammer; Mohammed Ahmed Hassan, Osman Mesaik; Smith, Colin; Choudhary, M. Iqbal.

In: Steroids, Vol. 86, 2014, p. 56-61.

Research output: Contribution to journalArticle

Baydoun, Elias ; Bano, Saira ; Atia-Tul-Wahab ; Jabeen, Almas ; Yousuf, Sammer ; Mohammed Ahmed Hassan, Osman Mesaik ; Smith, Colin ; Choudhary, M. Iqbal. / Fungal transformation and T-cell proliferation inhibitory activity of melengestrol acetate and its metabolite. In: Steroids. 2014 ; Vol. 86. pp. 56-61.
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