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

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

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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 2-128 mg/L and 0.5-128 mg/L, respectively. Hyperenone A also showed growth-inhibitory activity against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG at 75 mg/L and 100 mg/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.

Original languageEnglish
Pages (from-to)124-129
Number of pages6
JournalInternational Journal of Antimicrobial Agents
Volume39
Issue number2
Early online date10 Nov 2011
DOIs
Publication statusPublished - Feb 2012

Keywords

  • Hypercalin B
  • Hyperenone A
  • Hypericum acmosepalum
  • MurE ligase
  • Peptidoglycan
  • Staphylococcus aureus
  • Tuberculosis

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