The plant-derived chalcone Xanthoangelol targets the membrane of Gram-positive bacteria

Meier, Dieter; Vázquez‐Hernández, Melissa; Geelen, Lasse van; Muharini, Rini; Proksch, Peter; Bandow, Julia E.; Kalscheuer, Rainer

doi:10.1016/j.bmc.2019.115151

Cited by 29 publications

(22 citation statements)

References 29 publications

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“…Flavonoids share a common skeleton with the 15‐carbon 2‐phenyl‐chromone core (C6C3C6 system, Figure 1B), [ 38 ] which are further divided into nearly 20 groups. [ 33 ] Antibacterial activities of flavonoids have been controversially reported; [ 13,39,40 ] it remains unclear to what extent the side‐chain modification of flavonoids affects the activity. Since the presence of prenyl‐moiety can sharply increase the lipophilicity of natural products, [ 41,42 ] we hypothesized whether and how the prenylation modulates the activity of flavonoids through attachment to bacterial membrane.…”

Section: Resultsmentioning

confidence: 99%

Plant Natural Flavonoids Against Multidrug Resistant Pathogens

et al. 2021

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The increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens accelerate the desires for new antibiotics. Natural products dominate the preferred chemical scaffolds for the discovery of antibacterial agents. Here, the potential of natural flavonoids from plants against MDR bacteria, is demonstrated. Structure–activity relationship analysis shows the prenylation modulates the activity of flavonoids and obtains two compounds, α‐mangostin (AMG) and isobavachalcone (IBC). AMG and IBC not only display rapid bactericidal activity against Gram‐positive bacteria, but also restore the susceptibility of colistin against Gram‐negative pathogens. Mechanistic studies generally show such compounds bind to the phospholipids of bacterial membrane, and result in the dissipation of proton motive force and metabolic perturbations, through distinctive modes of action. The efficacy of AMG and IBC in four models associated with infection or contamination, is demonstrated. These results suggest that natural products of plants may be a promising and underappreciated reservoir to circumvent the existing antibiotic resistance.

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Section: Resultsmentioning

confidence: 99%

Plant Natural Flavonoids Against Multidrug Resistant Pathogens

et al. 2021

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“…Lysostaphin was used as a positive control, while linezolid, daptomycin, moxifloxacin, and DMSO served as negative controls. Using a Tecan Infinite M Plex plate reader, fluorescence intensity of the PI dye was measured every 5 min for 2 h at 535 nm excitation wavelength and 617 nm emission wavelength …”

Section: Experimental Sectionmentioning

confidence: 99%

Nature-Inspired (di)Azine-Bridged Bisindole Alkaloids with Potent Antibacterial In Vitro and In Vivo Efficacy against Methicillin-Resistant Staphylococcus aureus

et al. 2020

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Natural bisindole alkaloids such as Hyrtinadine A and Alocasin A, which are known to exhibit diverse bioactivities, provide promising chemical scaffolds for drug development. By optimizing the Masuda borylation–Suzuki coupling sequence, a library of various natural product-derived and non-natural (di)azine-bridged bisindoles was created. While unsubstituted bisindoles were devoid of antibacterial activity, 5,5′-chloro derivatives were highly active against methicillin-resistant Staphylococcus aureus (MRSA) and further Gram-positive pathogens at minimal inhibitory concentrations ranging from 0.20 to 0.78 μM. These compounds showed strong bactericidal killing effects but only moderate cytotoxicity against human cell lines. Furthermore, the two front-runner compounds 4j and 4n exhibited potent in vivo efficacy against MRSA in a mouse wound infection model. Although structurally related bisindoles were reported to specifically target pyruvate kinase in MRSA, antibacterial activity of 4j and 4n is independent of pyruvate kinase. Rather, these compounds lead to bacterial membrane permeabilization and cellular efflux of low-molecular-weight molecules.

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“…Flavonoid compounds have a basic skeleton with the 2-phenyl-chromone with C6-C3-C6 system (Graphic picture). The antibacterial effects of flavonoids have been previously reported [20,21]. Four typical flavonoids including baicalin, catechin, kaempferol, and quercetin (Table 1), which were abundant in plants were selected to assess the direct action to Staphylococcus aureus.…”

Section: Screening Of Flavonoids By the Antihemolytic Activitymentioning

confidence: 99%

Suppressing Alpha-Hemolysin as Potential Target to Screen of Flavonoids to Combat Bacterial Coinfection

Deng

Liang

et al. 2021

Molecules

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The rapid emergence of bacterial coinfection caused by cytosolic bacteria has become a huge threat to public health worldwide. Past efforts have been devoted to discover the broad-spectrum antibiotics, while the emergence of antibiotic resistance encourages the development of antibacterial agents. In essence, bacterial virulence is a factor in antibiotic tolerance. However, the discovery and development of new antibacterial drugs and special antitoxin drugs is much more difficult in the antibiotic resistance era. Herein, we hypothesize that antitoxin hemolytic activity can serve as a screening principle to select antibacterial drugs to combat coinfection from natural products. Being the most abundant natural drug of plant origins, flavonoids were selected to assess the ability of antibacterial coinfections in this paper. Firstly, we note that four flavonoids, namely, baicalin, catechin, kaempferol, and quercetin, have previously exhibited antibacterial abilities. Then, we found that baicalin, kaempferol, and quercetin have better inhibitions of hemolytic activity of Hla than catechin. In addition, kaempferol and quercetin, have therapeutic effectivity for the coinfections of Staphylococcus aureus and Pseudomonas aeruginosa in vitro and in vivo. Finally, our results indicated that kaempferol and quercetin therapied the bacterial coinfection by inhibiting S. aureus α-hemolysin (Hla) and reduced the host inflammatory response. These results suggest that antitoxins may play a promising role as a potential target for screening flavonoids to combat bacterial coinfection.

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The plant-derived chalcone Xanthoangelol targets the membrane of Gram-positive bacteria

Cited by 29 publications

References 29 publications

Plant Natural Flavonoids Against Multidrug Resistant Pathogens

Plant Natural Flavonoids Against Multidrug Resistant Pathogens

Nature-Inspired (di)Azine-Bridged Bisindole Alkaloids with Potent Antibacterial In Vitro and In Vivo Efficacy against Methicillin-Resistant Staphylococcus aureus

Suppressing Alpha-Hemolysin as Potential Target to Screen of Flavonoids to Combat Bacterial Coinfection

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