Share This Article:

Investigation of the Anti-Mycobacterial Mechanism of Action of 7-Methyljuglone

Abstract Full-Text HTML Download Download as PDF (Size:129KB) PP. 60-62
DOI: 10.4236/ojrd.2012.22009    3,498 Downloads   6,350 Views   Citations

ABSTRACT

Objectives: Although the naphthoquinone, 7-methyljuglone (7-MJ), is active against Mycobacterium tuberculosis (MTB) in vitro, neither the cellular site nor mechanism of anti-mycobacterial action of this agent has been identified. The primary objective of the current study was to investigate the mycobacterial outer membrane as a potential target of 7-MJ by measuring the effects of this agent (0.023 - 1.5 mg/L) on microbial ATP levels and uptake of K+ . Methods: Bioluminescence and radiometric (uptake of 86Rb+) procedures were used to assay microbial ATP levels and K+ transport respectively. Results: Exposure of MTB (strain H37Rv) to 7-MJ for 60 min resulted in dose-related decreases in both microbial ATP levels and uptake of 86Rb+ which achieved statistical significance (P < 0.05) at concentrations of 0.4 and 0.1 mg/L respectively. Conclusions: These observations are compatible with the mycobacterial membrane as being the putative site of action of 7-MJ, targeting microbial energy metabolism and K+ transport.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

V. Thaver, J. Meyer, R. Cockeran, M. Cholo, R. Anderson and N. Lall, "Investigation of the Anti-Mycobacterial Mechanism of Action of 7-Methyljuglone," Open Journal of Respiratory Diseases, Vol. 2 No. 2, 2012, pp. 60-62. doi: 10.4236/ojrd.2012.22009.

References

[1] M. A. De Groote and G. Huitt, “Infections Due to Rapidly Growing Mycobacteria,” Clinical Infectious Diseases, Vol. 42, No. 12, 2006, pp. 1756-1763. doi:10.1086/504381
[2] I. Stander and C. W. van Wyk, “Toothbrushing with the Root of Euclea Natlensis,” Journal de Biologie Buccale, Vol. 19, No. 2, 1991, pp. 167-172.
[3] L. M. van der Vijver and K. W. Gerritsma, “Naphthoquinones of Euclea and Diospyros Species,” Phytochemistry, Vol. 13, No. 10, 1974, pp. 2322-2323. doi:10.1016/0031-9422(74)85052-1
[4] N. Lall, J. J. Meyer, Y. Wang, N. B. Bapela, C. E. J. van Rensburg, B. Fourie and S. G. Franzblau, “Characterization of Intracellular Activity of Antitubercular Constituents the Roots of Euclea Natalensis,” Pharmaceutical Biology, Vol. 43, No. 4, 2005, pp. 353-357. doi:10.1080/13880200590951829
[5] M. C. Cholo, H. I. Boshoff, H. C. Steel, R. Cockeran, N. M. Matlola, K. J. Downing, V. Mizrahi and R. Anderson, “Effects of Clofazimine on Potassium Uptake by a Trk-Deletion Mutant of Mycobacterium Tuberculosis,” Journal of Antimicrobial Chemotherapy, Vol. 57, No. 1, 2006, pp. 79-84. doi:10.1093/jac/dki409
[6] V. M. Bulatovic, N. L. Wengenack, J. R. Uhl, L. Hall, G. D. Roberts, F. R. Cockerill 3rd and F. Rusnak, “Oxidative Stress Increases Susceptibility of Mycobacterium Tuberculosis to Isoniazid,” Antimicrobial Agents and Chemotherapy, Vol. 46, No. 9, 2002, pp. 2665-2671.
[7] L. F. Medina, P. F. Hertz, V. Stefani, J. A. Henriques, A. Zanotto-Filho and A. Brandelli, “Aminonaphthoquinone Induces Oxidative Stress in Staphylococcus Aureus,” Biochemistry and Cell Biology, Vol. 84, No. 5, 2006, pp. 720-727. doi:10.1139/o06-087
[8] T. Yano, S. Kassovska-Bratinova, S. J. Teh, J. Winkler, K. Sullivan, A. Isaacs, N. M. Schechter and H. Rubin, “Reduction of Clofazimine by Mycobacterial Type 2 NADH: Quinone Oxidoreductase: A Pathway for the Generation of Bactericidal Levels of Reactive Oxygen Species,” Journal of Biological Chemistry, Vol. 286, No. 12, 2011, pp. 10276-10287. doi:10.1074/jbc.M110.200501

  
comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.