title: 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.affiliation: Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, 29-39 Brunswick Square, Bloomsbury, London WC1N 1AX, UK.
authors.forename: Khadijo
authors.initials: K
authors.lastname: Osman
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Evangelopoulos
authors.forename: Chandrakala
authors.initials: C
authors.lastname: Basavannacharya
authors.forename: Antima
authors.initials: A
authors.lastname: Gupta
authors.forename: Timothy D
authors.initials: TD
authors.lastname: McHugh
authors.forename: Sanjib
authors.initials: S
authors.lastname: Bhakta
authors.forename: Simon
authors.initials: S
authors.lastname: Gibbons
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D020902:Hypericum / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009163:Mycobacterium bovis / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010453:Peptide Synthases / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D010453:Peptide Synthases; C554750:MurE protein, Mycobacterium tuberculosis
references.citation: BMJ. 2002 Dec 14;325(7377):1390-1
references.pmid: 12480853
references.citation: Fitoterapia. 2002 Jul;73(4):300-4
references.pmid: 12234572
references.citation: Chem Pharm Bull (Tokyo). 1985 Feb;33(2):557-64
references.pmid: 4017108
references.citation: J Ethnopharmacol. 2004 Feb;90(2-3):389-95
references.pmid: 15013206
references.citation: J Antimicrob Chemother. 2010 Oct;65(10):2101-7
references.pmid: 20719764
references.citation: Phytochemistry. 1995 Nov;40(5):1447-52
references.pmid: 8534402
references.citation: Chem Rev. 2005 Feb;105(2):759-74
references.pmid: 15700964
references.citation: J Ethnopharmacol. 2002 Jul;81(2):287-92
references.pmid: 12065165
references.citation: J Clin Microbiol. 2006 Feb;44(2):655-6
references.pmid: 16455939
references.citation: Tuberculosis (Edinb). 2010 Jan;90(1):16-24
references.pmid: 19945347
references.citation: Bioorg Med Chem. 2009 Mar 1;17(5):1884-9
references.pmid: 19223185
references.citation: J Antimicrob Chemother. 1989 Dec;24(6):851-62
references.pmid: 2559912
references.citation: Dis Mon. 2004 Jul;50(7):395-406
references.pmid: 15280870
references.citation: J Infect Dis. 2007 Aug 15;196 Suppl 1:S28-34
references.pmid: 17624823
references.citation: Protein Cell. 2010 Nov;1(11):1011-22
references.pmid: 21153518
references.citation: Bioorg Chem. 2009 Dec;37(6):217-22
references.pmid: 19804894
references.citation: J Pharm Pharmacol. 2001 May;53(5):583-600
references.pmid: 11370698
references.citation: J Antimicrob Chemother. 2002 Jun;49(6):999-1005
references.pmid: 12039892
references.citation: Clin Infect Dis. 2004 Oct 1;39(7):1010-5
references.pmid: 15472854
references.citation: Nature. 2011 Jan 27;469(7331):483-90
references.pmid: 21270886
references.citation: Antimicrob Agents Chemother. 1993 May;37(5):1086-94
references.pmid: 8517696
references.citation: Phytother Res. 2000 Mar;14(2):139-40
references.pmid: 10685116