Antibacterial Acylphloroglucinols from <i>Hypericum olympicum</i>

Shiu, Winnie Ka Po; Rahman, M. Mukhlesur; Curry, J C; Stapleton, Paul; Zloh, Mire; Malkinson, John P.; Gibbons, Simon

doi:10.1021/np2003319

Cited by 63 publications

(63 citation statements)

References 19 publications

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“…The challenge is to find new approaches to overcome antibiotic resistance and, particularly, antibiotic-resistant Gram-negative bacteria, whose outer membrane already precludes the use of many drugs that are effective against Grampositive pathogens. Thus, some investigators are focusing on natural products derived from nonconventional sources, such as plants (10,11), marine microorganisms (12), and insects (13). Another strategy involves making new chemical derivatives of existing antibiotics, on the basis of the rational design of the compounds using information such as the three-dimensional structure of the antibiotic (14,15), or linking drugs to peptides that can pass through membranes to facilitate their entry into the cell (16).…”

Section: Discussionmentioning

confidence: 99%

Synergistic Interactions of Vancomycin with Different Antibiotics against Escherichia coli: Trimethoprim and Nitrofurantoin Display Strong Synergies with Vancomycin against Wild-Type E. coli

Zhou

Kang

Yuan

et al. 2015

Antimicrob Agents Chemother

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Gram-negative bacteria are normally resistant to the antibiotic vancomycin (VAN), which cannot significantly penetrate the outer membrane. We used Escherichia coli mutants that are partially sensitive to VAN to study synergies between VAN and 10 other antibiotics representing six different functional categories. We detected strong synergies with VAN and nitrofurantoin (NTR) and with VAN and trimethoprim (TMP) and moderate synergies with other drugs, such as aminoglycosides. These synergies are powerful enough to show the activity of VAN against wild-type E. coli at concentrations of VAN as low as 6.25 g/ml. This suggests that a very small percentage of exogenous VAN does enter E. coli but normally has insignificant effects on growth inhibition or cell killing. We used the results of pairwise interactions with VAN V ancomycin (VAN) has proved to be an effective antibiotic against certain multidrug-resistant Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA). However, the large size of this glycopeptide precludes it from being useful against Gram-negative bacterial infections, since the outer membrane of Gram-negative bacteria acts as a barrier to its entry into the cell (1). Finding agents that act synergistically with VAN against Gram-negative bacteria would be valuable in treating infections caused by multidrug-resistant pathogens, such as carbapenem-resistant Klebsiella pneumoniae, a leading cause of hospitalacquired pneumonia in the United States (2). Certain mutants of Escherichia coli with gene knockouts that affect outer membrane assembly (surA [3] and smpA [4] mutants) display increased sensitivity to VAN. Recently, we have found that E. coli mutants lacking deoxycytidine deaminase (DCD) also are more sensitive to VAN than wild-type (WT) strains (5). In the work reported here, we have used surA and dcd mutants to study drug interactions between VAN and a series of antibiotics in E. coli. We detected strong synergies between VAN and nitrofurantoin (NTR) and between VAN and trimethoprim (TMP). We then tested different concentrations of each of these two antibiotics both alone and in combination with VAN in the wild-type background and demonstrated that wild-type cells are sensitized to relatively low concentrations of VAN in the presence of subinhibitory concentrations of either NTR or TMP. We discuss the possible implications of these results for combination drug therapy. MATERIALS AND METHODSE. coli strains. The DCD-deficient and SurA-deficient strains used here are from the Keio Collection, described by Baba et al. (6), and were made from the starting strain BW25113 (7). This starting strain (lacI q rrnB T14 ⌬lacZ WJ16 hsdR514 ⌬araBAD AH33 ⌬rhaBAD LD78 ) is used as the WT in the experiments reported here, unless otherwise stated. BW25113 is closely related to MG1655, as both are derived from the strain W1485 background (6). The dcd mutant and the surA mutant carry a complete deletion of the dcd gene and the surA gene, respectively, with a kan kanamycin resistance gene ...

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Section: Discussionmentioning

confidence: 99%

Synergistic Interactions of Vancomycin with Different Antibiotics against Escherichia coli: Trimethoprim and Nitrofurantoin Display Strong Synergies with Vancomycin against Wild-Type E. coli

Zhou

Kang

Yuan

et al. 2015

Antimicrob Agents Chemother

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“…321 One antibacterial acylphloroglucinol, olympicin D 549, was isolated and characterized from the aerial parts of Hypericum olympicum. 322 A hydroperoxyquinolone alkaloid, glycopentaphyllone 550, was reported from the fruits of Glycosmis pentaphylla, whose absolute configuration was established by applying Mosher's method. 323 Walsuronoid A 551 was the first limonoid with a peroxide linkage from Walsura robusta.…”

Section: Othersmentioning

confidence: 99%

Peroxy natural products

Liu

2013

Nat. Prod. Bioprospect.

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“…Professor Simon Gibbons [42] has done extensive work on the genus Hypericum, by exploring this genus as a lead source of antibacterial secondary metabolites with potential activity against S. aureus. Bioassayguided research on some Hypericum species led to the isolation of new acylphloroglucinols [29,43,44], norlignans [45], and xanthone [45] with potential activity against S. aureus. An acylphologlucinol, (S)-4,6-dihydroxy-2-O-(3 00 ,7 00 -dimethyl-2 00 ,6 00 -octadienyl)-1-(2'-methylbutanoyl)benzene (trivial name olympicin A; Figure 23.3), reported from Hypericum olympicum, revealed very potent (MICs of 1 mg/mL) activity against some clinical isolates of multidrug-resistant (MDR) and MRSA [43].…”

Section: Plant-derived Antimicrobial Secondary Metabolitesmentioning

confidence: 99%

“…Bioassayguided research on some Hypericum species led to the isolation of new acylphloroglucinols [29,43,44], norlignans [45], and xanthone [45] with potential activity against S. aureus. An acylphologlucinol, (S)-4,6-dihydroxy-2-O-(3 00 ,7 00 -dimethyl-2 00 ,6 00 -octadienyl)-1-(2'-methylbutanoyl)benzene (trivial name olympicin A; Figure 23.3), reported from Hypericum olympicum, revealed very potent (MICs of 1 mg/mL) activity against some clinical isolates of multidrug-resistant (MDR) and MRSA [43]. Hyperenone A (Figure 23.3), a constituent of Hypericum acmosepalum [44], revealed antibacterial activity against Staphylococcus aureus and M. tuberculosis and also inhibited the adenosine triphosphate-dependent MurE ligase of M. tuberculosis, a crucial enzyme for peptidoglycan biosynthesis.…”

Section: Plant-derived Antimicrobial Secondary Metabolitesmentioning

confidence: 99%

Antimicrobial Secondary Metabolites—Extraction, Isolation, Identification, and Bioassay

Rahman

2015

Evidence-Based Validation of Herbal Medicine

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Antibacterial Acylphloroglucinols from Hypericum olympicum

Cited by 63 publications

References 19 publications

Synergistic Interactions of Vancomycin with Different Antibiotics against Escherichia coli: Trimethoprim and Nitrofurantoin Display Strong Synergies with Vancomycin against Wild-Type E. coli

Synergistic Interactions of Vancomycin with Different Antibiotics against Escherichia coli: Trimethoprim and Nitrofurantoin Display Strong Synergies with Vancomycin against Wild-Type E. coli

Peroxy natural products

Antimicrobial Secondary Metabolites—Extraction, Isolation, Identification, and Bioassay

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