New anti-inflammatory metabolites by microbial transformation of medrysone

Saira Bano, Atia Tul Wahab, Sammer Yousuf, Almas Jabeen, Osman Mesaik Mohammed Ahmed Hassan, Atta Ur Rahman, M. Iqbal Choudhary

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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,and8. 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,and8 strongly inhibited the proliferation of T-cells with IC50 values between 50 <0.2 μg/mL), whereas compounds 2, 3, and 6 showed moderate levels of inhibition (IC50 =14.6-20.0 μg/mL). Compounds 1,and7 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.

Original languageEnglish
Article numbere0153951
JournalPLoS One
Volume11
Issue number4
DOIs
Publication statusPublished - 1 Apr 2016
Externally publishedYes

Fingerprint

Metabolites
Inhibitory Concentration 50
Anti-Inflammatory Agents
metabolites
inhibitory concentration 50
T-cells
Cunninghamella
Cytokines
T-Lymphocytes
Rhizopus
3T3 Cells
Neurospora crassa
Zymosan
cytokines
Respiratory Burst
T-lymphocytes
Cells
Phagocytes
Rhizopus stolonifer
X-Ray Diffraction

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bano, S., Wahab, A. T., Yousuf, S., Jabeen, A., Mohammed Ahmed Hassan, O. M., Rahman, A. U., & Choudhary, M. I. (2016). New anti-inflammatory metabolites by microbial transformation of medrysone. PLoS One, 11(4), [e0153951]. https://doi.org/10.1371/journal.pone.0153951

New anti-inflammatory metabolites by microbial transformation of medrysone. / Bano, Saira; Wahab, Atia Tul; Yousuf, Sammer; Jabeen, Almas; Mohammed Ahmed Hassan, Osman Mesaik; Rahman, Atta Ur; Choudhary, M. Iqbal.

In: PLoS One, Vol. 11, No. 4, e0153951, 01.04.2016.

Research output: Contribution to journalArticle

Bano, S, Wahab, AT, Yousuf, S, Jabeen, A, Mohammed Ahmed Hassan, OM, Rahman, AU & Choudhary, MI 2016, 'New anti-inflammatory metabolites by microbial transformation of medrysone', PLoS One, vol. 11, no. 4, e0153951. https://doi.org/10.1371/journal.pone.0153951
Bano S, Wahab AT, Yousuf S, Jabeen A, Mohammed Ahmed Hassan OM, Rahman AU et al. New anti-inflammatory metabolites by microbial transformation of medrysone. PLoS One. 2016 Apr 1;11(4). e0153951. https://doi.org/10.1371/journal.pone.0153951
Bano, Saira ; Wahab, Atia Tul ; Yousuf, Sammer ; Jabeen, Almas ; Mohammed Ahmed Hassan, Osman Mesaik ; Rahman, Atta Ur ; Choudhary, M. Iqbal. / New anti-inflammatory metabolites by microbial transformation of medrysone. In: PLoS One. 2016 ; Vol. 11, No. 4.
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