Spectroscopic characterization and efflux pump modulation of a thiophene curcumin derivative

Oliveira, Mauro Macêdo de; Santos, Hélcio Silva dos; Coutinho, Henrique Douglas Melo; Bandeira, Paulo Nogueira; Silva, Priscila T. da; Freitas, Thiago Sampaio de; Rocha, Janaína Esmeraldo; Xavier, Jayze da Cunha; Campina, Fábia F.; Barbosa, Cristina R.S.; Neto, José B. Araújo; Pereira, Raimundo Luiz Silva; Silva, Maria M.C.; Muniz, Débora Feitosa; Teixeira, Alexandre Magno Rodrigues; Frota, Vanessa Moreira; Rodrigues, Tigressa Helena Soares; Amado, Ana M.; Marques, M. P. M.; Carvalho, Luís A. E. Batista de; Nogueira, C.E.S.

doi:10.1016/j.molstruc.2020.128291

Cited by 18 publications

(4 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The furanochromones make close contact with most of these, as can be seen in the protein-ligand interaction diagram in Figure 4 . 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 ].…”

Section: Resultsmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

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

View full text Add to dashboard Cite

show abstract

“…The NorA protein model was created using the same procedure as described in Oliveira et al [18]. The model was then uploaded to the Molprobity [19] service for protonation.…”

Section: Methodsmentioning

confidence: 99%

ADMET study, spectroscopic characterization and effect of synthetic nitro chalcone in combination with norfloxacin, ciprofloxacin, and ethidium bromide against Staphylococcus aureus efflux pumps

Rocha¹,

Freitas²,

Xavier³

et al. 2022

Fundamemntal Clinical Pharma

Self Cite

View full text Add to dashboard Cite

Chalcones are present in a wide variety of plants, having in their structure two aromatic rings that are linked together by a chain composed of three carbon atoms with α, β‐unsaturated to carbonyl system. Bacteria have several drug resistance mechanisms, among them the efflux pump; this mechanism, when active, is able to expel different compounds from inside bacterial cells. Several efflux pumps have already been identified for Staphylococcus aureus bacteria, including MepA and NorA. Many chalcones have been isolated and identified with various activities, such as antimicrobial. In view of this, this article aimed to evaluate the antibiotic modifying effect of chalcone (E)‐1‐(2‐hydroxyphenyl)‐3‐(3‐nitrophenyl)prop‐2‐en‐1‐one against S. aureus carrier of NorA and MepA efflux pump. Regarding the antibiotic, there was a synergism when associated with ciprofloxacin in SA‐K2068 strain, showing this chalcone as an alternative to reverse the resistance to this medicine. The physicochemical properties calculated were fundamental in the description of the predicted pharmacokinetic properties. Despite the mutagenic risk caused by the metabolic activation of nitrochalcone, it is possible to notice a pharmacological principle in a longer half‐life for the performance of biological activities. The compound has a good bioavailability, as it is highly absorbed in the intestine and easily transported by plasma proteins, in addition to not presenting neurotoxic, hepatotoxic, and cardiotoxic damage.

show abstract

“…Following the methods of Oliveira et al [58] and Freitas et al [59], the sequences of the NorA efflux pump from S. aureus 1199 (code Q03325) and MepA from S. aureus NCTC 8325 (code Q2G140), obtained from the UniProt database, were selected to build the three-dimensional models (3D) of proteins by homology, using the SWISS-MODEL server [60]. From the 50 templates available for each efflux pump, we chose the best model for each: PDB identifiers 7lo8 and 3wbn, respectively.…”

Section: Molecular Dockingmentioning

confidence: 99%

3-Substituted Coumarins Inhibit NorA and MepA Efflux Pumps of Staphylococcus aureus

Araújo-Neto,

Oliveira-Tintino,

de Araújo

et al. 2023

Antibiotics

View full text Add to dashboard Cite

Coumarins are compounds with scientifically proven antibacterial properties, and modifications to the chemical structure are known to improve their effects. This information is even more relevant with the unbridled advances of antibiotic resistance, where Staphylococcus aureus and its efflux pumps play a prominent role. The study’s objective was to evaluate the potential of synthetic coumarins with different substitutions in the C-3 position as possible inhibitors of the NorA and MepA efflux pumps of S. aureus. For this evaluation, the following steps took place: (i) the determination of the minimum inhibitory concentration (MIC); (ii) the association of coumarins with fluoroquinolones and ethidium bromide (EtBr); (iii) the assessment of the effect on EtBr fluorescence emission; (iv) molecular docking; and (v) an analysis of the effect on membrane permeability. Coumarins reduced the MICs of fluoroquinolones and EtBr between 50% and 87.5%. Coumarin C1 increased EtBr fluorescence emission between 20 and 40% by reinforcing the evidence of efflux inhibition. The molecular docking results demonstrated that coumarins have an affinity with efflux pumps and establish mainly hydrogen bonds and hydrophobic interactions. Furthermore, C1 did not change the permeability of the membrane. Therefore, we conclude that these 3-substituted coumarins act as inhibitors of the NorA and MepA efflux pumps of S. aureus.

show abstract

Spectroscopic characterization and efflux pump modulation of a thiophene curcumin derivative

Cited by 18 publications

References 37 publications

Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus

Modulation of Drug Resistance by Furanochromones in NorA Overexpressing Staphylococcus Aureus

ADMET study, spectroscopic characterization and effect of synthetic nitro chalcone in combination with norfloxacin, ciprofloxacin, and ethidium bromide against Staphylococcus aureus efflux pumps

3-Substituted Coumarins Inhibit NorA and MepA Efflux Pumps of Staphylococcus aureus

Contact Info

Product

Resources

About