Evaluation of antibacterial activity and reversal of the NorA and MepA efflux pump of estragole against Staphylococcus aureus bacteria

Costa, Roger Henrique Sousa da; Rocha, Janaína Esmeraldo; Freitas, Thiago Sampaio de; Pereira, Raimundo Luiz Silva; Pereira, Francisco; Oliveira, Maria Rayane Correia de; Batista, Francisco Lucas Alves; Coutinho, Henrique Douglas Melo; Menezes, Irwin Rose Alencar de

doi:10.1007/s00203-021-02347-x

Cited by 20 publications

(15 citation statements)

References 31 publications

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“…Not only that but a previous study described a chalcone with NorA inhibition properties that interacts with Arg310 through a hydrogen bond [ 55 ]. There are also imidazolines EPIs that bind to this same region of the binding site and interact with Arg310 through hydrogen bonds [ 19 ]. Interaction through H-bond with Arg310 also was reported to aminoguanidine hydrazones [ 7 , 56 ].…”

Section: Resultsmentioning

confidence: 99%

“…Resistance-modifying agents/modulators are compounds that potentiate the activity of an antibiotic against resistant strains, and some of these agents may act as efflux pump inhibitors (EPIs), as in the case of several naturally occurring compounds from plants [12][13][14][15][16]. Various phytocompounds have been studied for its ability to inhibit S. aureus efflux pumps, including terpenes such as eugenol [17], carvacrol, thymol [18], estragole [19], α-pinene, and limonene [20]. Inhibition of NorA has also been reported for ferulic acid and its esterified derivatives [21], chalcones [22], and vitamin K3 [23].…”

Section: Introductionmentioning

confidence: 99%

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Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus

Rodrigues

Borges

Nogueira

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Khellin and visnagin are natural furanochromones that photoreact with DNA. Khellin has been used in the treatment of vitiligo and psoriasis, as well as in the treatment of angina pectoris and asthma due to its potent action as a coronary vasodilator and antispasmodic agent. The present study aimed to investigate whether the compounds khellin and visnagin act as inhibitors of NorA protein, an efflux pump overproduced by the strain of Staphylococcus aureus SA-1199B that confers resistance to the fluoroquinolones, such as norfloxacin and ciprofloxacin. These substances alone did not show antibacterial activity against the strain tested. On the other hand, when these compounds were added to the culture medium at subinhibitory concentration, they were able to reduce the minimum inhibitory concentration (MIC) of norfloxacin, ethidium bromide, as well as berberine, suggesting that these compounds are modulating agents of norfloxacin resistance, possibly due to NorA inhibition. Molecular docking analysis showed that both khellin and visnagin form hydrogen bonds with Arg310, an important residue in the interaction between NorA and its substrates, supporting the hypothesis that these compounds are NorA inhibitors. These results suggest a possible application of khellin and visnagin as adjuvants to norfloxacin in the treatment of infections caused by strains of S. aureus that overproduce NorA.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus

Rodrigues

Borges

Nogueira

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…Therefore, the NorA pump and other efflux pumps are attractive targets to many studies [ 93 – 98 ]. The present study along with previous studies [ 93 – 98 ] showed that the potential antibacterial antibiofilm activities as well as the inhibited NorA efflux pump were because of the compounds' molecular docking mechanisms. The compounds' activity correlated with physicochemical properties, such as positive charge, aromatic ring, and hydrophobic interactions of the compounds with the efflux pump, which is mediated by hydrogen bonds.…”

Section: Resultsmentioning

confidence: 99%

“…Particularly, the NorA efflux pump in S.aureus was related to virulence, biofilm formation, and resistance to diverse drugs, especially fluoroquinolone (e.g., ciprofloxacin), quinolones, verapamil, and omeprazole, in addition to biocides, dyes, quaternary ammonium compounds, and antiseptics [89][90][91][92]. erefore, the NorA pump and other efflux pumps are attractive targets to many studies [93][94][95][96][97][98]. e present study along with previous studies [93][94][95][96][97][98] showed that the potential antibacterial antibiofilm activities as well as the inhibited NorA efflux pump were because of the compounds' molecular docking mechanisms.…”

Section: Effect Of the New Hydantoin Compounds On S Aureusmentioning

confidence: 99%

Effect of New 2-Thioxoimidazolidin-4-one Compounds against Staphylococcus aureus Clinical Strains and Immunological Markers’ Combinations

Subhi

Fatah

Muhammad

2022

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Although the structure-activity relationship indicates that the 4-thioxoimidazolidin ring is essential for antibacterial activities and pharmaceutical applications, there were no enough studies on the derivatives of this compound. Evaluating the new hydantoin compounds C5 (3-((2-bromobenzylidene) amino)-2- thioxoimidazolidin-4-one) and C6 (3-((4- methoxybenzylidene) amino)-2-thioxoimidazolidin-4-one) that were prepared against clinical Staphylococcus aureus isolates for antibacterial, antibiofilm, and antihemagglutination activities is the aim of this study. Therefore, the potential clinical resistance of the strains was evaluated by their ability to form biofilms, antibiotic resistance, and agglutinate erythrocytes macroscopically and microscopically; besides, the bacterial biofilm was screened for any association with the patient’s serum immunoglobulin levels and complements. Despite the effective concentration for C5 and C6 compounds, which is ≤ 31.25 μg/ml, the reduction rate is not concentration-dependent; it depends on the molecular docking of the hydantoin compounds. Hence, the effect of the minimal inhibitory concentrations (MICs) is variable. In this study, the results for the compounds (with the concentration of 31.25–62.5 μg/mL for C5 and 62.5–125 μg/mL for C6) significantly manifest the antibacteria, antibiofilm, and antihemagglutination effects against the virulent strains of S. aureus due to the high percentage of biofilm inhibition that was caused by the new hydantoin compounds. Besides, time-kill kinetics studies showed that these compounds pose bactericidal action. Overall, this study revealed that the new hydantoin derivatives have an interesting potential as new antibacterial drugs through the inhibition of bacterial adhesion. The infections of these isolates activate the complement system through the lectin pathway. Nevertheless, these compounds can be improved in order to be used at even lower concentrations.

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“…As a result, both gallic acid and caffeic acid could lead to a reversal of antimicrobial resistance, with the latter inhibiting both MRSA and Nor-A of RN4220 and 1199B. Besides that, many previous studies have demonstrated that antibacterial resistance is significantly mediated by various natural products and semisynthetic derivatives, suggesting potential break resistance by adjuvants [ 16 – 21 ]. These substances showed a solid ability to increase the activity of inhibitors towards MDR bacteria, with a lower MIC of antibiotics and/or Nor-A pump substrates (such as ethidium bromide or benzalkonium chloride) upon coadministration.…”

Section: Introductionmentioning

confidence: 99%

Chalcone Derivatives as Potential Inhibitors of P-Glycoprotein and NorA: An In Silico and In Vitro Study

Trinh

Ngo

et al. 2022

BioMed Research International

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The human P-glycoprotein (P-gp) and the NorA transporter are the major culprits of multidrug resistance observed in various bacterial strains and cancer cell lines, by extruding drug molecules out of the targeted cells, leading to treatment failures in clinical settings. Inhibiting the activity of these efflux pumps has been a well-known strategy of drug design studies in this regard. In this manuscript, our earlier published machine learning models and homology structures of P-gp and NorA were utilized to screen a chemolibrary of 95 in-house chalcone derivatives, identifying two hit compounds, namely, F88 and F90, as potential modulators of both transporters, whose activity on Staphylococcus aureus strains overexpressing NorA and resistant to ciprofloxacin was subsequently confirmed. The findings of this study are expected to guide future research towards developing novel potent chalconic inhibitors of P-gp and/or NorA.

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Evaluation of antibacterial activity and reversal of the NorA and MepA efflux pump of estragole against Staphylococcus aureus bacteria

Cited by 20 publications

References 31 publications

Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus

Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus

Effect of New 2-Thioxoimidazolidin-4-one Compounds against Staphylococcus aureus Clinical Strains and Immunological Markers’ Combinations

Chalcone Derivatives as Potential Inhibitors of P-Glycoprotein and NorA: An In Silico and In Vitro Study

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