A Clerodane Diterpene from <i>Callicarpa americana</i> Resensitizes Methicillin-Resistant <i>Staphylococcus aureus</i> to β-Lactam Antibiotics

Dettweiler, Micah; Melander, Roberta J.; Porras, Gina; Risener, Caitlin J.; Marquez, Lewis; Samarakoon, Tharanga; Quave, Cassandra L.

doi:10.1021/acsinfecdis.0c00307

Cited by 22 publications

(20 citation statements)

References 34 publications

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“…There is a growing recognition in the field that the pursuit of single active compounds through bioassay-guided fractionation is not sufficient to capture the potential of plant compounds as antibacterials-synergy and other interactions must be studied (Caesar and Cech, 2019). In addition to the study of interactions within plant extracts, many recent innovations involve finding plant compounds that synergize with existing antibiotics, particularly as resistance-modifying agents for use against drug-resistant bacteria (Abreu et al, 2012;Abreu et al, 2017;Dettweiler et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

A Systematic Review of Plants With Antibacterial Activities: A Taxonomic and Phylogenetic Perspective

et al. 2021

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Background: Antimicrobial resistance represents a serious threat to human health across the globe. The cost of bringing a new antibiotic from discovery to market is high and return on investment is low. Furthermore, the development of new antibiotics has slowed dramatically since the 1950s’ golden age of discovery. Plants produce a variety of bioactive secondary metabolites that could be used to fuel the future discovery pipeline. While many studies have focused on specific aspects of plants and plant natural products with antibacterial properties, a comprehensive review of the antibacterial potential of plants has never before been attempted.Objectives: This systematic review aims to evaluate reports on plants with significant antibacterial activities.Methods: Following the PRISMA model, we searched three electronic databases: Web of Science, PubMed and SciFinder by using specific keywords: “plant,” “antibacterial,” “inhibitory concentration.”Results: We identified a total of 6,083 articles published between 1946 and 2019 and then reviewed 66% of these (4,024) focusing on articles published between 2012 and 2019. A rigorous selection process was implemented using clear inclusion and exclusion criteria, yielding data on 958 plant species derived from 483 scientific articles. Antibacterial activity is found in 51 of 79 vascular plant orders throughout the phylogenetic tree. Most are reported within eudicots, with the bulk of species being asterids. Antibacterial activity is not prominent in monocotyledons. Phylogenetic distribution strongly supports the concept of chemical evolution across plant clades, especially in more derived eudicot families. The Lamiaceae, Fabaceae and Asteraceae were the most represented plant families, while Cinnamomum verum, Rosmarinus vulgaris and Thymus vulgaris were the most studied species. South Africa was the most represented site of plant collection. Crude extraction in methanol was the most represented type of extraction and leaves were the main plant tissue investigated. Finally, Staphylococcus aureus was the most targeted pathogenic bacteria in these studies. We closely examine 70 prominent medicinal plant species from the 15 families most studied in the literature.Conclusion: This review depicts the current state of knowledge regarding antibacterials from plants and provides powerful recommendations for future research directions.

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Section: Introductionmentioning

confidence: 99%

A Systematic Review of Plants With Antibacterial Activities: A Taxonomic and Phylogenetic Perspective

et al. 2021

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“…As mentioned above, the bioactivity of plant extracts, as complex mixtures of different classes of natural compounds, is often better than the bioactivity of a single isolated bioactive compound [ 4 , 5 , 6 , 7 ]. However, it is important to know which compounds are the carriers of these activities.…”

Section: Resultsmentioning

confidence: 99%

“…Natural compounds from plant extracts can synergize by targeting multiple receptors, facilitating transport to a target, and offering protection from degradation as well as modification of resistance [ 4 ]. Although it is difficult to prove the activity of the compounds in complex mixtures, synergistic interactions in plant extracts are evidenced by the frequent loss of activity upon fractionation [ 5 , 6 , 7 ]. However, only 20% of known plants have been investigated in pharmaceutical studies [ 8 ], and still many species must be inspected.…”

Section: Introductionmentioning

confidence: 99%

Exploring New Sources of Bioactive Phenolic Compounds from Western Balkan Mountains

Karalija

Dahija

Demir

et al. 2022

Plants

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This study presents the first report on phenolic composition and bioactivity of ethanolic extracts of three plant species that grow in the western Balkan mountains and are used in traditional folk medicine: Valeriana montana, Salix retusa, and Campanula hercegovina. Phenolics were extracted from different aerial plant parts using 80% ethanol to assess the possibility of sustainable use of these plants as a source of bioactive compounds without disruption to the roots (for V. montana) or destruction of whole habitats (for S. retusa and C. hercegovina). The ethanolic extract of V. montana flower contained noticeable levels of apigenin and quercetin. The branches and bark of S. retusa were significantly rich in catechin, while rutin was the major phenolic found in the leaf extract of C. hercegovina. Furthermore, the flower extract of V. montana revealed the best antioxidant activity, which was comparable to 4-hydroxybenzoic acid and quercetin. Considering antimicrobial activity, the leaf extracts of V. montana and C. hercegovina demonstrated potent activity against all microbes tested, while the extracts of S. retusa were moderately effective. The presented results emphasize the potential of these plants as novel sources of bioactive compounds.

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“…We recently disclosed the adjuvant activity of the diterpene natural product 12( S ),16ϵ‐dihydroxycleroda‐3,13‐dien‐15,16‐olide ((−)‐ 1 ), which we refer to as (−)‐LZ‐2112 for short, isolated from the American beautyberry, Callicarpa americana . (−)‐ 1 potentiated the β‐lactam antibiotic oxacillin against MRSA (FICI=0.125), lowering the minimum inhibitory concentration (MIC) below the susceptibility break point against several clinically relevant strains [6] . While there have been other reports of synergism between clerodanes and oxacillin against MRSA, the primary focus of these studies has been on their use as antibiotics not adjuvants, and development of the scaffold has not been probed [7] .…”

Section: Methodsmentioning

confidence: 99%

“…The crystal structure clearly shows an ( R ) configuration at C‐12 of 14 . Due to the stereochemical divergence created during the furan addition, this leads us to infer that the material isolated from C. americana 1 does indeed possess an ( S ) configuration at C‐12 [6] …”

Section: Methodsmentioning

confidence: 99%

Synthesis, Stereochemical Confirmation, and Derivatization of 12(S),16ϵ‐Dihydroxycleroda‐3,13‐dien‐15,16‐olide, a Clerodane Diterpene That Sensitizes Methicillin‐Resistant Staphylococcus aureus to β‐Lactam Antibiotics

et al. 2022

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Over the past decades, antibiotic resistance has grown to a point where orthogonal approaches to combating infections caused by resistant bacteria are needed. One such approach is the development of nonmicrobicidal small molecules that potentiate the activity of conventional antibiotics, termed adjuvants. The diterpene natural product 12(S),16ɛ-dihydroxycleroda-3,13-dien-15,16-olide, which we refer to as (À )-LZ-2112, is known to synergize with oxacillin against methicillinresistant Staphylococcus aureus (MRSA). To explore this activity, (À )-LZ-2112 was synthesized and the structure confirmed through X-ray analysis. Preliminary structure-activity relationship studies following the synthesis of several analogs identified key structural elements responsible for activity and indicate that scaffold simplification is possible. A preliminary mode of action study suggests mecA plays a role in the adjuvant activity of (À )-LZ-2112.

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A Clerodane Diterpene from Callicarpa americana Resensitizes Methicillin-Resistant Staphylococcus aureus to β-Lactam Antibiotics

Cited by 22 publications

References 34 publications

A Systematic Review of Plants With Antibacterial Activities: A Taxonomic and Phylogenetic Perspective

A Systematic Review of Plants With Antibacterial Activities: A Taxonomic and Phylogenetic Perspective

Exploring New Sources of Bioactive Phenolic Compounds from Western Balkan Mountains

Synthesis, Stereochemical Confirmation, and Derivatization of 12(S),16ϵ‐Dihydroxycleroda‐3,13‐dien‐15,16‐olide, a Clerodane Diterpene That Sensitizes Methicillin‐Resistant Staphylococcus aureus to β‐Lactam Antibiotics

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