MICROBIAL OXIDATION OF FINASTERIDE WITH MACROPHOMINA PHASEOLINA(KUCC 730)

Saira Erum; Sadia Sultan; Syed Adnan Ali Shah; Muhammad Ashraf; Muhammad Iqbal Choudhary

doi:10.22159/ijpps.2017v9i11.13576

Authors

Saira Erum H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
Sadia Sultan Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia
Syed Adnan Ali Shah Atta-ur-Rahman Institute for Natural Products Discovery (AuRIns), Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia
Muhammad Ashraf Pharmaceutical and Life Sciences Core, Universiti Teknologi MARA, Shah Alam, 40450 Shah Alam, Selangor Darul Ehsan, Malaysia
Muhammad Iqbal Choudhary H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan

DOI:

https://doi.org/10.22159/ijpps.2017v9i11.13576

Keywords:

Microbial transformation, Finateride, Oxidised metabolites, Macrophomina phaseolina

Abstract

Objectives: New Â microbial oxidative derivatives of Finasteride [17Î²-(N-tert-butylcarbamoyl)-4-aza-5Î±-androst-1-en-3-one] (1) has been investigated with Macrophomina phaseolina (ATCC730).

Methods: Fermented media of Â Macrophomina phaseolina (ATCC730) was prepared to cultivate the fungal cultures . Substrate 1 was incubated in liquid media for 16 days. After sixteen days, filtration and extraction of the fermented media was carried out with 9 L DCM in three portions. Resulting organic extract was dried using anhydrous (Na2SO4), and evaporated to afford a brown gum (950 mg). This on chromatographic purification with MeOH in CH2Cl2 afforded the metabolites 2-4 .

Results: Three oxidised metabolites of finasteride (1) which were identified as 15-oxo-finasteride (2), 11a-hydroxyfinasteride (3), and 15Î²-hydroxyfinasteride (4). Metabolite 2 was found to be new. The structure of the oxidised metabolites were elucidated by 1-D (¹H, ¹³C) and 2-D NMR (COSY, HMBC, HMQC, NOESY) techniques and MS analyses.

Conclusion: As a result of these study, oxidation at C-7, C-11 and C-15 positions were found. Metabolite 2 was identified as a new metabolite.

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