Triketones active against antibiotic-resistant bacteria: Synthesis, structure–activity relationships, and mode of action

Klink, John W. van; Larsen, Lesley; Perry, Nigel B.; Weavers, Rex T.; Cook, Gregory M.; Bremer, Phil; MacKenzie, Andrew; Kirikae, Teruo

doi:10.1016/j.bmc.2005.07.045

Cited by 71 publications

(78 citation statements)

References 37 publications

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“…18,19) Briefly, The tested strains were cultivated in mueller-hinton broth medium for bacteria at 37°C. Chloromycetin was used as a positive control.…”

Section: Energy Minimization and Ecd Calculationsmentioning

confidence: 99%

Antibacterial Meroterpenoids from the South China Sea Sponge <i>Dysidea</i> sp.

Zhang

Huang

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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Key words meroterpenoid; marine sponge; antibacterial activity; DysideaMarine organisms such as sponges represent a largely unexploited source of a wide variety of natural meroterpenoids.1) Sponges of the genus Dysidea are a rich source of bioactive meroterpenoids, the majority of which are sesquiterpene quinones/quinols.2) This class of compounds frequently consist of sesquiterpene moieties linked to quinones, quinols, or structural analogues.3) The sesquiterpene unit is of biosynthetic interest, as it usually features a drimane-or a 4,9-friedodrimane-type skeleton comprising a trans-or a less common cis-fused ring junction.3) These compounds have attracted much interest due to their structural diversity and varied biological activities, including anti-human immunodeficiency virus (HIV), 4) antibacterial, 5) antifungal, 6) antioxidative, 7) antitumor, 8) anti-inflammatory, 9) inhibition against protein tyrosine kinase (PTK) and protein tyrosine phosphatase 1B (PTP1B), 10,11) and activation of hypoxia-inducible factor-1 (HIF-1) activities. 12)During our search for bioactive metabolites from tropical sponges, we encountered a purple-colored encrusting Dysidea sp. off the south China sea. The crude extract of this sponge showed significant antibacterial activity against Staphylococcus aureus (25923) with the minimum inhibitory concentration (MIC) value of 25 µg/mL. Chemical investigation of bioactive extracts of this sponge led to the isolation of three new sesquiterpene phenols (1−3) and one new sesquiterpene aminoquinone (4), together with four known sesquiterpene derivatives (5−8). Herein, we report the details of the purification and structure elucidation of these compounds, as well as the evaluation of antibacterial activity (Fig. 1). Results and Discussion

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“…18,19) Briefly, The tested strains were cultivated in mueller-hinton broth medium for bacteria at 37°C. Chloromycetin was used as a positive control.…”

Section: Energy Minimization and Ecd Calculationsmentioning

confidence: 99%

Antibacterial Meroterpenoids from the South China Sea Sponge <i>Dysidea</i> sp.

Zhang

Huang

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Recentemente, van Klink relatou uma relação estruturaatividade de alguns floroglucinóis e suas tricetonas correspondentes, mostrando que estas substâncias são mais ativas contra bactérias Gram positivas que Gram negativas e que as atividades estão relacionadas com as características hidrofóbicas e interações intramoleculares de ligações de hidrogênio. 18 O teste de bioautografia revelou que substâncias com diferentes Rfs foram responsáveis pela inibição do crescimento de S. aureus ATCC 25923 e um MRSA pertencente ao clone CEB. O isolamento bioguiado, a purificação e identificação por EM e RMN de 1 H e 13 C levaram à obtenção das substâncias 1, 2 e 3, responsáveis pelas propriedades antibacterianas.…”

Section: Resultsunclassified

Atividade antibacteriana de floroglucinóis e do extrato hexânico de Hypericum brasiliense Choysi

França¹,

Kuster²,

Rito³

et al. 2009

Quím. Nova

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Recebido em 10/10/07; aceito em 11/12/08; publicado na web em 28/4/09 ANTIBACTERIAL ACTIVITY OF THE PHLOROGLUCINOLS AND HEXANIC EXTRACT FROM Hypericum brasiliense Choysi. Three phloroglucinols were obtained from Hypericum brasiliense: japonicine A (1), isouliginosin B (2) and uliginosin B (3). Bioautography and disk diffusion methods were used to determine antibacterial activity of the hexanic extract. Strains of the Coagulase Negative Staphylococcus and American Methicillin Resistant Staphylococcus aureus clones showed a growth inhibition zone ranging from 10 to 12 mm and 7 to 15 mm, respectively. Minimal inhibitory concentration (MIC) values were used to measure antistaphylococcal activity for all phloroglucinols. Isouliginosin B and uliginosin B presented MIC values of 1.5 and 3.0 µg/mL, respectively, while japonicine A displayed MIC value of 50.0 µg/mL. Keywords: Hypericum brasiliense; antibacterial activity; phloroglucinol. O gênero Hypericum é representado por 420 espécies pertencentes à família das Clusiaceae (Guttiferae). Esta família é composta por espécies com importantes efeitos farmacológicos e biológicos tais como antibacteriano, antiviral, antioxidante, atividade citótoxica e antidepressiva. 3,4 O Hypericum perforatum é a espécie medicinal mais reconhecida, amplamente estudada e utilizada no tratamento de depressão leve a moderada. 5 Alguns estudos clínicos e experimentais propõem que o mecanismo de ação parece estar relacionado com o bloqueio não seletivo da recaptação de serotonina, noradrenalina e dopamina. Os efeitos antidepressivos são devidos especialmente à hiperforina, um derivado de floroglucinol. 6 Outros derivados de floroglucinóis, conjugados com o ácido filicínico, demonstraram excelente atividade antiestafilocócica, podendo-se considerar o gênero Hypericum como uma fonte de moléculas com potencial atividade antibacteriana. 7 No Brasil, a família Clusiaceae é representada por 21 gêneros e 183 espécies, sendo o Hypericum brasiliense o mais estudado. 4 Esta planta é um arbusto bianual, encontrada nas regiões sul e sudeste do Brasil 8 e é usada na medicina tradicional com propriedades antiespasmódicas e no tratamento de doenças infecciosas. 9 O H. brasiliense é quimicamente constituído de flavonóides, xantonas e floroglucinóis derivados do ácido filicínico com significativos efeitos farmacológicos e biológicos. Observou-se que as xantonas apresentaram efeito de inibição sobre a enzima monoamina oxidase (MAO), assim como atividade antifúngica, e o extrato hidroalcoólico mostrou atividades analgésica em ratos e antidepressiva. 10 Considerando que os derivados de floroglucinóis isolados de H. brasiliense são responsáveis pela atividade antibacteriana, 10 o objetivo deste trabalho foi o isolamento bioguiado destas substâncias por métodos cromatográficos. Em paralelo, a atividade do extrato hexano contra MRSA de diferentes regiões do continente americano, assim como MRCNS isolados de pacientes hospitalares, foi investigada. Além disto, também foram avaliadas as atividades dos floroglucinóis is...

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“…Times range from 10-30 h. The resulting solution is evaporated to dryness under reduced pressure and the solid residue taken up in distilled water. This solution is extracted with CH 2 Cl 2 , and the organic layer dried over Na 2 SO 4 . The solvent is evaporated under reduced pressure and the crude fluorinated ketone purified by radial chromatography.…”

Section: General Procedures For the Preparation Of Trifluoromethyl-β-dmentioning

confidence: 99%

“…For example, indanone derivatives have anticoagulant properties and are used in elaborating latent fingerprints, bindone variants comprise components of near infrared dyes while certain tetralones and naphthones, ketones similar in structure to those shown in Figure 1, have demonstrated bioactive properties [1][2][3][4][5][6]. Since bioactivity is known to be enhanced in many classes of fluorinated molecules [3,7], it is desirous to prepare fluorine-containing molecules with similar architecture and gain a better understanding of their structure-property relationships.…”

Section: Introductionmentioning

confidence: 99%

Novel Fluorinated Indanone, Tetralone and Naphthone Derivatives: Synthesis and Unique Structural Features

Sloop

Boyle

Fountain³

et al. 2012

Applied Sciences

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Several fluorinated and trifluoromethylated indanone, tetralone and naphthone derivatives have been prepared via Claisen condensations and selective fluorinations in yields ranging from 22-60%. In addition, we report the synthesis of new, selectively fluorinated bindones in yields ranging from 72-92%. Of particular interest is the fluorination and trifluoroacetylation regiochemistry observed in these fluorinated products. We also note unusual transformations including a novel one pot, dual trifluoroacetylation, trifluoroacetylnaphthone synthesis via a deacetylation as well as an acetyl-trifluoroacetyl group exchange. Solid-state structural features exhibited by these compounds were investigated using crystallographic methods. Crystallographic results, supported by spectroscopic data, show that trifluoroacetylated ketones prefer a chelated cis-enol form whereas fluorinated bindone products exist primarily as the cross-conjugated triketo form. OPEN ACCESSAppl. Sci. 2012, 2 62

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Triketones active against antibiotic-resistant bacteria: Synthesis, structure–activity relationships, and mode of action

Cited by 71 publications

References 37 publications

Antibacterial Meroterpenoids from the South China Sea Sponge <i>Dysidea</i> sp.

Antibacterial Meroterpenoids from the South China Sea Sponge <i>Dysidea</i> sp.

Atividade antibacteriana de floroglucinóis e do extrato hexânico de Hypericum brasiliense Choysi

Novel Fluorinated Indanone, Tetralone and Naphthone Derivatives: Synthesis and Unique Structural Features

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