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

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 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.

• Authors: Khadijo Osman, Dimitrios Evangelopoulos, Chandrakala Basavannacharya, Antima Gupta, Timothy D McHugh, Sanjib Bhakta, Simon Gibbons
• Journal: International journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 39 Issue 2 Pg. 124-9 (Feb 2012) ISSN: 1872-7913 [Electronic] Netherlands
• PMID: 22079533 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• Enzyme Inhibitors
• Plant Extracts
• Peptide Synthases
• MurE protein, Mycobacterium tuberculosis

Topics

• Anti-Bacterial Agents (chemistry, isolation & purification, pharmacology)
• Bacterial Proteins (antagonists & inhibitors)
• Enzyme Inhibitors (chemistry, isolation & purification, pharmacology)
• Escherichia coli (drug effects)
• Hypericum (chemistry)
• Magnetic Resonance Spectroscopy
• Mass Spectrometry
• Microbial Sensitivity Tests
• Molecular Structure
• Mycobacterium bovis (drug effects)
• Mycobacterium tuberculosis (drug effects)
• Peptide Synthases (antagonists & inhibitors)
• Plant Extracts (chemistry, isolation & purification, pharmacology)
• Staphylococcus aureus (drug effects)