Skip to main content
SpringerLink
Log in

Biotransformation of Celecoxib Using Microbial Cultures

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Microbial transformation studies can be used as models to simulate mammalian drug metabolism. In the present investigation, biotransformation of celecoxib was studied in microbial cultures. Bacterial, fungal, and yeast cultures were employed in the present study to elucidate the metabolism of celecoxib. The results indicate that a number of microorganisms metabolized celecoxib to various levels to yield eight metabolites, which were identified by high-performance liquid chromatography diode array detection and liquid chromatography tandem mass spectrometry analyses. HPLC analysis of biotransformed products indicated that majority of the metabolites are more polar than the substrate celecoxib. The major metabolite was found to be hydroxymethyl metabolite of celecoxib, while the remaining metabolites were produced by carboxylation, methylation, acetylation, or combination of these reactions. The methyl hydroxylation and further conversion to carboxylic acid was known to occur in metabolism by mammals. The results further support the use of microorganisms for simulating mammalian metabolism of drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Smith, R. V., & Rosazza, J. P. (1975). Journal of Pharmaceutical Sciences, 11, 1737–1759.

    Article  Google Scholar 

  2. Smith, R.V. and Rosazza, J.P. (1982) In J. P. Rosazza (Ed.), Microbial transformations of bioactive compounds (pp.1–42). Boca Raton: CRC

  3. Smith, R. V., & Rosazza, J. P. (1983). Journal of Natural Products, 46, 79–91.

    Article  CAS  Google Scholar 

  4. Clark, A. M., McChesney, J. D., & Hufford, C. D. (1985). Medicinal Research Reviews, 5, 231–253.

    Article  CAS  Google Scholar 

  5. Clark, A. M., & Hufford, C. D. (1991). Medicinal Research Reviews, 11, 473–501.

    Article  CAS  Google Scholar 

  6. Abourashed, E. A., Clark, A. M., & Hufford, C. D. (1999). Current Medicinal Chemistry, 6, 359–374.

    CAS  Google Scholar 

  7. Ferris, J. P., MacDonald, L. H., Patrie, M. A., & Martin, M. A. (1976). Archives of Biochemistry and Biophysics, 175, 443–452.

    Article  CAS  Google Scholar 

  8. Venisetty, R. K., & Ciddi, V. (2003). Current Pharmaceutical Biotechnology, 4, 123–140.

    Article  Google Scholar 

  9. Paulson, S. K., Hribar, J. D., Liu, N. W. K., Hajdu, E., Bible, R. H., Jr., Piergies, A., et al. (2000). Drug Metabolism and Disposition, 28, 308–314.

    CAS  Google Scholar 

  10. Paulson, S. K., Zhang, J. Y., Breau, A. P., Hribar, J. D., Liu, N. W. K., Jessen, S. M., et al. (2000). Drug Metabolism and Disposition, 28, 514–521.

    CAS  Google Scholar 

  11. Backhus, L. M., Petasis, N. A., Uddin, J., Schonthal, A. H., Bart, R. D., Lin, Y., et al. (2005). J. Journal of Thoracic and Cardiovascular Surgery, 130, 1406–1412.

    Article  CAS  Google Scholar 

  12. Pyrko, P., Soriano, N., Kardosh, A., Liu, Y. T., Uddin, J., Petasis, N. A., et al. (2006). Mol. Cancer, 5, 19.

    Google Scholar 

  13. Abbate, F., Coetzee, A., Casini, A., Ciattini, S., Scozzafava, A., & Supuran, C. T. (2004). Bioorganic & Medicinal Chemistry Letters, 14, 337–341.

    Article  CAS  Google Scholar 

  14. Solomon, S.D., McMurray, J.J.V., Pfeffer, M.A., Wittes, J., Fowler, R., Finn, P., Anderson, W.F., Zauber, A., Hawk, E. and Bertagnolli, M. (2005) New Eng. J. Med. 352, 1071–1080.

    Article  CAS  Google Scholar 

  15. Venisetty, R. K., Keshetty, S., & Ciddi, V. (2004) Abstract 64th International Pharmaceutical Federation Congress, New Orleans, p. 16.

  16. Jayasagar, G., Kumar, M. K., Chandrasekhar, K., Prasad, P. S., & Rao, Y. M. (2002). Pharmazie, 57, 619–621.

    CAS  Google Scholar 

  17. Cha, C. J., Doerge, D. R., & Cerniglia, C. E. (2001). Applied and Environmental Microbiology, 67, 4358–4360.

    Article  CAS  Google Scholar 

  18. Zhang, D., Evans, F. E., Freeman, J. P., Yang, Y., Deck, J., & Cerniglia, C. E. (1996). Chemico-Biological Interactions, 102, 79–92.

    Article  CAS  Google Scholar 

  19. Duhart, B. T., Zhang, D., Deck, J., Freeman, J. P., & Cerniglia, C. E. (1999). Xenobiotica, 29, 733–746.

    Article  CAS  Google Scholar 

  20. Hansen, E. B., Jr., Heflich, R. H., Korfmacher, W. A., Miller, D. W., & Cerniglia, C. E. (1988). Journal of Pharmaceutical Sciences, 77, 259–264.

    Article  CAS  Google Scholar 

  21. Zhang, J. Y., Wang, Y. F., Dudkowski, C., Yang, D., Chang, M., Yuan, J., et al. (2000). Journal of Mass Spectrometry, 35, 1259–1270.

    Article  CAS  Google Scholar 

  22. Otten, S., & Rosazza, J. P. (1981). Journal of Natural Products, 44, 562–568.

    Article  CAS  Google Scholar 

  23. Sariaslani, F. S., & Rosazza, J. P. (1985). Applied and Environmental Microbiology, 49, 451–452.

    CAS  Google Scholar 

  24. Hufford, C. D., Lee, I. S., ElSohly, H. N., Chi, H. T., & Baker, K. T. (1990). Pharmaceutical Research, 7, 923–967.

    Article  CAS  Google Scholar 

  25. Freitag, D. G., Foster, R. T., Coutts, R. T., Pickard, M. A., & Pasutto, F. M. (1997). Drug Metabolism and Disposition, 25, 685–692.

    CAS  Google Scholar 

  26. Huang, H., Yang, X., Li, Q., Sun, L., & Zhong, D. (2006). Applied Microbiology and Biotechnology, 72, 486–491.

    Article  CAS  Google Scholar 

  27. Penning, T. D., Talley, J. T., Bertenshaw, S. R., Carter, J. S., Collins, P. W., Docter, S., et al. (1997). Journal of Medicinal Chemistry, 40, 1347–1365.

    Article  CAS  Google Scholar 

  28. Sandberg, M., Yasar, U., Stromberg, P., Hoog, J. O., & Eliasson, E. (2002). British Journal of Clinical Pharmacology, 54, 423–429.

    Article  CAS  Google Scholar 

  29. Schwartz, H., Liebig-Weber, A., Hochstätter, H., & Böttcher, H. (1996). Applied Microbiology and Biotechnology, 44, 731–735.

    Article  CAS  Google Scholar 

  30. Mazier, C., Jaouen, M., Sari, M., & Buisson, D. (2004). Bioorganic & Medicinal Chemistry Letters, 14, 5423–5426.

    Article  CAS  Google Scholar 

  31. Mountfield, R. J., & Hopper, D. J. (1998). Applied Microbiology and Biotechnology, 50, 379–383.

    Article  CAS  Google Scholar 

  32. Rosi, D., Peruzotti, G., Dennis, E. W., Berberian, D. A., Freele, H., Tullar, B. F., et al. (1967). Journal of Medicinal Chemistry, 10, 867–876.

    Article  CAS  Google Scholar 

  33. Schwartz, H., Licht, R. E., & Radunz, H. E. (1993). Applied Microbiology and Biotechnology, 40, 382–385.

    Article  CAS  Google Scholar 

  34. Zhang, D., Zhang, H., Aranibar, N., Hanson, R., Huang, Y., Cheng, P. T., et al. (2006). Drug Metabolism and Disposition, 34, 267–280.

    Article  CAS  Google Scholar 

  35. Clark, A. M., Hufford, C. D., & McChesney, J. D. (1981). Antimicrobial Agents and Chemotherapy, 19, 337–341.

    CAS  Google Scholar 

  36. Clark, A. M., Evans, S. L., Hufford, C. D., & McChesney, J. D. (1982). Journal of Natural Products, 45, 574–581.

    Article  CAS  Google Scholar 

  37. Foster, G. R., Coutts, R. T., Pasutto, F. M., & Mozayani, A. (1988). Life Sciences, 42, 285–292.

    Article  CAS  Google Scholar 

  38. Foster, B. C., Wilson, D. L., & McGilveray, I. J. (1989). Xenobiotica, 19, 445–452.

    Article  CAS  Google Scholar 

  39. Foster, G. R., Lister, D. L., Zamecnic, J., & Coutts, R. T. (1991). Canadian Journal of Microbiology, 37, 791–795.

    Article  CAS  Google Scholar 

  40. Wetzstein, H. G., Stadler, M., Tichy, H. V., Dalhoff, A., & Karl, W. (1999). Applied and Environmental Microbiology, 65, 1556–1563.

    CAS  Google Scholar 

  41. Parshikov, I. A., Freeman, J. P., Lay, J. O., Jr., Beger, R. D., Williams, A. J., & Sutherland, J. B. (1999). FEMS Microbiology Letters, 177, 131–135.

    Article  CAS  Google Scholar 

  42. Pal, M., Madan, M., Padakanti, S., Pattabiraman, V. R., Kalleda, S., Vanguri, A., et al. (2003). Journal of Medicinal Chemistry, 46, 3975–3984.

    Article  CAS  Google Scholar 

  43. Dirikolu, L., Lehner, A. F., Jacobs, J., Woods, W. E., Karpiesiuk, W., Harkins, J. D., Carter, W. G., Boyles, J., Hughes, C. G., Bosken, J. M., Holtz, C., Natrass, C., Fisher, M., Tobin, T. (2000) Proceedings of the 13th International Conference of Racing Analysts and Veterinarians, Cambridge, pp. 162–170.

Download references

Acknowledgments

The authors are thankful to Dr. Ramesh Mullangi and Mr. Raja Reddy Kallem, Discovery Research, Dr. Reddy’s Laboratories, Hyderabad for LC–MS/MS spectral analysis. The work was carried out with the financial assistance from University Grants Commission, New Delhi and Council of Scientific & Industrial Research, New Delhi.

Author information

Authors and Affiliations

  1. University College of Pharmaceutical Sciences, Kakatiya University, Warangal, 506009, Andhra Pradesh, India

    Keshetty Srisailam & Ciddi Veeresham

Authors
  1. Keshetty Srisailam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ciddi Veeresham
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ciddi Veeresham.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Srisailam, K., Veeresham, C. Biotransformation of Celecoxib Using Microbial Cultures. Appl Biochem Biotechnol 160, 2075–2089 (2010). https://doi.org/10.1007/s12010-009-8789-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-009-8789-3

Keywords

Search

Navigation