Skip to main content
SpringerLink
Log in

Inhibition of Beta-Lactamase by 1,4-Naphthalenedione from the Plant Holoptelea integrifolia

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

Abstract

The most important mechanism of the beta-lactam antibiotic resistance is the destruction of the antibiotics by the enzyme beta-lactamase. Use of beta-lactamase inhibitors in combination with antibiotics is one of the successful antibacterial strategies. The inhibitory effect of a phytochemical, 1,4-naphthalenedione, isolated from the plant Holoptelea integrifolia on beta-lactamase is reported here. This compound was found to have a synergistic effect with the antibiotic amoxicillin against a resistant strain of Staphylococcus aureus. The enzyme was purified from the organism and incubated with the compound. An assay showed that the compound can inhibit the enzymatic activity of beta-lactamase. Modeling and molecular docking studies indicated that the compound can fit into the active site of beta-lactamase. Hence, the compound can serve as a potential lead compound for the development of effective beta-lactamase inhibitor that can be used against beta-lactam-resistant microbial strains.

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
Fig. 5

Similar content being viewed by others

References

  1. Barlett, J. G. (2004). Pocket book of infectious disease therapy. London: Lippincott Williams and Wilkins.

    Google Scholar 

  2. Chambers, H. F., & Neu, H. C. (1995). Penicillins. In G. L. Mandell, J. E. Bennett & R. Dolin (Eds.), Principles and practice of infectious disease (pp. 233–246). New York: Churchill Livingstone.

    Google Scholar 

  3. Moellering, R. C. (1993). Meeting the challenges of beta-lactamases. The Journal of Antimicrobial Chemotherapy, 31, 1–8. doi:10.1093/jac/31.1.1.

    Article  CAS  Google Scholar 

  4. Garcia-Rodrignez, J. A., & Jones, R. N. (2002). Antimicrobial resistance in gram-negative isolates from European intensive care unit: data from the Meropenem Yearly Susceptibility Test information Collection (MYSTIC) programme. Journal of Chemotherapy (Florence, Italy), 14, 25–32.

    Google Scholar 

  5. Charles, W., & Stratton, M. D. (1996). Antimicrobics and infectious diseases. News Letter, 15, 51–53.

    Google Scholar 

  6. Bush, K. (1988). Beta-lactamase inhibitors from laboratory to clinic. Clinical Microbiology Reviews, 1, 109–123.

    CAS  Google Scholar 

  7. Hutchison, L. C., & Norman, R. A. (2003). Antibiotics and resistance in dermatology: focus on treating the elderly. Dermatologic Therapy, 16, 206–213. doi:10.1046/j.1529-8019.2003.01630.x.

    Article  Google Scholar 

  8. Betoni, J. E. C., Mantovani, R. P., Barbosa, L. N., Di Stasi, L. C., & Fernandes, A., Jr. (2006). Synergism between plant extract and antimicrobial drugs used on S. aureus diseases. Memorias do Instituto Oswaldo Cruz, Rio de Janeiro, 101, 387–390.

    Google Scholar 

  9. Zygmunt, D. J., Stratton, C. W., & Kernodle, D. S. (1992). Characterization of four beta-lactamases produced by Staphylococcus aureus. Antimicrobial Agents and Chemotherapy, 36, 440–445.

    CAS  Google Scholar 

  10. Jagtap, S. B., Patil, N. N., Kupadnis, B. P., & Kulkarni, B. A. (2001). Characterization and antimicrobial activity of Erbium (III) Complexes of C-3 Substituted 2-hydroxy-1, 4-naphthalenedione-1-oxime derivatives. Journal of Metal Based Drugs, 8, 159–164.

    Article  CAS  Google Scholar 

  11. Ball, M. D., Bartlett, M. S., Shaw, M., Smith, J. W., Nasr, M., & Meshnick, S. R. (2001). Activities and conformational fitting of 1, 4-naphthoquinone derivatives and other cyclic 1, 4-diones tested in vitro against Pneumocystis carinii. Antiicrobial Agents and Chemotherapy, 45, 1473–1479.

    Article  CAS  Google Scholar 

  12. Lowry, O. H., Rosebrough, N. J., Farr, A. L., & Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. The Journal of Biological Chemistry, 193, 265–275.

    CAS  Google Scholar 

  13. Livermore, D. M., & Yang, Y. J. (1987). Beta-lactamase lability and inducer power of newer beta-lactam antibiotics in relation to their activity against beta-lactamase inducibility mutants of P. aeruginosa. The Journal of Infectious Diseases, 155, 775–782.

    CAS  Google Scholar 

  14. Perret, C. J. (1995). Iodometric assay of penicillinase. Nature, 174, 1012–1013. doi:10.1038/1741012a0.

    Article  Google Scholar 

  15. Halgren, T. A. (1996). Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. Journal of Computational Chemistry, 17, 490–519. doi:10.1002/(SICI)1096-987X(199604)17:5/6<490::AID-JCC1>3.0.CO;2-P.

    Article  CAS  Google Scholar 

  16. Fletcher, R. (1980). Practical methods of optimization: Unconstrained optimization (pp. 417–436). New York: Wiley.

    Google Scholar 

  17. Brooks, B. R., Bruccoleri, R. E., Olafson, B. D., States, D. J., Swaminathan, S., & Karplus, M. (1983). CHARMM: a program for macromolecular energy minimization and dynamics calculations. Journal of Computational Chemistry, 4, 187–217. doi:10.1002/jcc.540040211.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The Bioinformatics Infrastructure Facility (funded by the Department of Biotechnology, Government of India) in the department is gratefully acknowledged for providing the computational facility.

Author information

Authors and Affiliations

  1. Department of Biotechnology and Microbiology, Kannur University, Thalassery Campus, Palayad P. O., Kannur, Kerala, 670661, India

    N. V. Vinod, R. Shijina, K. V. Dileep & C. Sadasivan

Authors
  1. N. V. Vinod
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Shijina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. V. Dileep
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Sadasivan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Sadasivan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vinod, N.V., Shijina, R., Dileep, K.V. et al. Inhibition of Beta-Lactamase by 1,4-Naphthalenedione from the Plant Holoptelea integrifolia . Appl Biochem Biotechnol 160, 1752–1759 (2010). https://doi.org/10.1007/s12010-009-8656-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-009-8656-2

Keywords

Search

Navigation