An antibacterial from Hypericum acmosepalum inhibits ATP-dependent MurE ligase from Mycobacterium tuberculosis

Osman, Khadijo; Evangelopoulos, Dimitrios; Basavannacharya, Chandrakala; Gupta, Antima; McHugh, Timothy D.; Bhakta, Sanjib; Gibbons, Simon

doi:10.1016/j.ijantimicag.2011.09.018

« Previous Next »International Journal of Antimicrobial Agents
Volume 39, Issue 2 , Pages 124-129, February 2012

An antibacterial from Hypericum acmosepalum inhibits ATP-dependent MurE ligase from Mycobacterium tuberculosis

Khadijo Osman
- Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, 29–39 Brunswick Square, Bloomsbury, London WC1N 1AX, UK
- Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, Bloomsbury, London WC1E 7HX, UK
Dimitrios Evangelopoulos
- Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, Bloomsbury, London WC1E 7HX, UK
- Centre for Clinical Microbiology, Department of Infection, Royal Free Campus, University College London, London NW3 2PF, UK
Chandrakala Basavannacharya
- Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, Bloomsbury, London WC1E 7HX, UK
Antima Gupta
- Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, Bloomsbury, London WC1E 7HX, UK
Timothy D. McHugh
- Centre for Clinical Microbiology, Department of Infection, Royal Free Campus, University College London, London NW3 2PF, UK
Sanjib Bhakta
- Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, Malet Street, Bloomsbury, London WC1E 7HX, UK
- Corresponding author. Tel.: +44 207 631 6355; fax: +44 207 631 6246.
Simon Gibbons
- Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, 29–39 Brunswick Square, Bloomsbury, London WC1N 1AX, UK
- Corresponding author. Tel.: +44 207 753 5913; fax: +44 207 753 5909.

Received 27 June 2011; accepted 21 September 2011. published online 14 November 2011.

Abstract

In a project to characterise new antibacterial chemotypes from plants, hyperenone A and hypercalin B were isolated from the hexane and chloroform extracts of the aerial parts of Hypericum acmosepalum. The structures of both compounds were characterised by extensive one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and were confirmed by mass spectrometry. Hyperenone A and hypercalin B exhibited antibacterial activity against multidrug-resistant strains of Staphylococcus aureus, with minimum inhibition concentration ranges of 2–128mg/L and 0.5–128mg/L, respectively. Hyperenone A also showed growth-inhibitory activity against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG at 75mg/L and 100mg/L. Neither hyperenone A nor hypercalin B inhibited the growth of Escherichia coli and both were non-toxic to cultured mammalian macrophage cells. Both compounds were tested for their ability to inhibit the ATP-dependent MurE ligase of M. tuberculosis, a crucial enzyme in the cytoplasmic steps of peptidoglycan biosynthesis. Hyperenone A inhibited MurE selectively, whereas hypercalin B did not have any effect on enzyme activity.