MICROBIAL OXIDATION OF FINASTERIDE WITH MACROPHOMINA PHASEOLINA(KUCC 730)


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

Abstract


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

Methods: Fermented media of  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 15β-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.


Keywords


Microbial transformation, Finateride, Oxidised metabolites, Macrophomina phaseolina

| PDF | HTML |

References


. G. H. Rasmusson, G. F. Reynolds, N. G. Steinberg, E. Walton, G. F. Patel, T. Liang,

M. A Cascier, A. H. Cheung, J. R Brooks, C.Berman, J. Med. Chem. 27 (1984) 1690.

. S. Heizl, Med. Monatsschr Pharm. 22(4) (1999) 124.

. T. J. Murtola, T. L. J. Tammela, L. Maattanen, M. Hakama, A. Auvinen, Eur. J.

Cancer. 43 (2007) 775.

. E. S. Venkataramani, J. R. Carlin, U. Dolling, P. Christofalo, R. J.Magliette,

B. H. Arison, R. A. Stearns, Analys New York Academy of Sciences, (1994) 745.

. C. Pamidi, Q. Jia, WO Patent. (1998) 9850419.

. S. B. Mahato, I. Mazumder, Phytochemistry. 34 (1995) 883.

. D. Arthan, J. Svasti, P. Kittakoop, D. Pittayakhachonwut, M.Tanticharoen,

Y. Thebtaranonth, Phytochemistry. 59 (2002), 459.

. Y. Q. Zhang, D.Q. Wang, Microbiology, 33 (2) (2006) 142.

. H. C. Murray, D. H. Peterson, U.S. Patent, 2602769 (1952).

. P. Fernandes, A. Cruz, B. Angelova, H. M. Pinheiro, J. M. S. Cabral, Enzyme

Microb. Tech. 32 (2003) 688.

. M.I. Choudhary, M. Atif, S.A.A. Shah, S. Sultan, Int. J. Pharm. Pharm. Sci. 7 (1) (2015) 385-388.

. M. Atif, S.A.A. Shah, S. Sultan, M.I. Choudhary, Int. J. Pharm. Pharm. Sci. 7(4) (2015) 104-107.

. S. Sultan, M. Zaimi, E.H. Anouar, S.A.A. Shah, F. Salim, R. Rahim, Z. Bashir, K.A. Trabolsy, J.F.F. Weber, Molecules 19 (2014) 13775-13787.

. M.I. Choudhary, M. Atif, S.A.A. Shah, S. Sultan, S. Erum, S. N. Khan, Atta-ur-Rahman, Int. J. Pharm. Pharm. Sci. 6 (7) (2014) 375-378.

. M.I. Choudhary, M. Atif, S. Sultan, S.A.A. Shah, Atta-ur-Rahman, Int. J. Pharm. Pharm. Sci. 6 (11) (2014) 195-198.

. S.A.A. Shah, S. Sultan, N.B .Hassan, F.K.B. Muhammad, M.A.B.M. Faridz, F.B.M. Hussain, M. Hussain, H.S. Adnan, Steroids 78 (2013) 1312–1324.

. S.A.A. Shah, S. Sultan, H.S. Adnan, Int. J. Pharm. Pharm. Sci. 3 Suppl 1 (2011) 1-6.

. M.I. Choudhary, S. Sultan, S. Jalil, S. Anjum, Atta-ur-Rahman, H. K. Fun, Chem biodivers, 2 (2005) 392-400.

. M. I. Choudhary, S. Sultan, M. T. H. Khan, Atta-ur-Rahman, Steroids, 70 (2005) 798-802.

. M.I. Choudhary, S. Sultan, M. Yaqoob, Musharraf, S.G. A. Yasin, Shaheen, F. Atta-ur-Rahman Nat Prod Res, 17 (2003) 389-395.

. M.I. Choudhary, S. Sultan, Hassan, M.T. Khan, A. Yasin, F. Shaheen, Atta-ur-Rahman. Nat Prod Res, 18 (2004). 529-535.

. S. Sultan, M.I. Choudhary, S. N. Khan, U. Fatima, M. Atif, R. A. Ali, M. Q. Fatmi, Eur J Med Chem. 62 (2013) 764–770.

. Sultan S, Ghani NA, Shah SAA, Ismail NH, Noor MZ, Naz H. (2013). Microbial transformation of anthraquinones-A Review. Biosci Biotechnol Res Asia,10(2), 577-582.

. S.A.A. Shah, S. Sultan, H.S. Adnan, Orient. J. Chem. 29(2) (2013) 389-403

. S.A.A.Shah, H.L. Tan, S. Sultan, M.A.B.M Faridz,. M.A.B.M. Shah, S. Nurfazilah, Hussain, M, Int. J. Mol. Sci. 15 (2014). 12027-12060.

. S.A.A. Shah, S. Sultan, M. Zaimi, J. Mol. Struct. 1042 (2013) 118–122.




About this article

Title

MICROBIAL OXIDATION OF FINASTERIDE WITH MACROPHOMINA PHASEOLINA(KUCC 730)

Keywords

Microbial transformation, Finateride, Oxidised metabolites, Macrophomina phaseolina

DOI

10.22159/ijpps.2017v9i11.13576

Date

01-11-2017

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 11, 2017 Page: 17-20

Online ISSN

0975-1491

Statistics

67 Views | 17 Downloads

Authors & Affiliations

Saira Erum
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
Malaysia

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


Article Tools



Refbacks

  • There are currently no refbacks.