Synthesis, structural, characterization, antibacterial and antibiotic modifying activity, ADMET study, molecular docking and dynamics of chalcone (<i>E</i>)-1-(4-aminophenyl)-3-(4-nitrophenyl)prop-2-en-1-one in strains of <i>Staphylococcus aureus</i> carrying NorA and MepA efflux pumps
Creators: name: de Souza, Mikael Amaro
name: Rodrigues, Leilane Gomes
name: Rocha, Janaina Esmeraldo
name: de Freitas, Thiago Sampaio
name: Bandeira, Paulo Nogueira
name: Marinho, Márcia Machado
name: da Rocha, Matheus Nunes
name: Marinho, Emmanuel Silva
name: Barreto, Antonio Cesar Honorato
name: Coutinho, Henrique Douglas Melo
name: Silva, Lorena Mara Alexandre
name: da Silva Julião, Murilo Sergio
name: Canuto, Kirley Marques
name: da Fonseca, Aluísio Marques
name: Teixeira, Alexandre Magno Rodrigues
name: dos Santos, Hélcio Silva
Publisher: name: Taylor & Francis
Year: 2023
Subjects: Biochemistry
Pharmacology
Chemical Sciences not elsewhere classified
Biological Sciences not elsewhere classified

description: Chalcones have an open chain flavonoid structure that can be obtained from natural sources or by synthesis and are widely distributed in fruits, vegetables, and tea. They have a simple and easy to handle structure due to the α-β-unsaturated bridge responsible for most biological activities. The facility to synthesize chalcones combined with its efficient in combating serious bacterial infections make these compounds important agents in the fight against microorganisms. In this work, the chalcone (<i>E</i>)-1-(4-aminophenyl)-3-(4-nitrophenyl)prop-2-en-1-one (HDZPNB) was characterized by spectroscopy and electronic methods. In addition, microbiological tests were performed to investigate the modulator potential and efflux pump inhibition on <i>S. aureus</i> multi-resistant strains. The modulating effect of HDZPNB chalcone in association with the antibiotic norfloxacin, on the resistance of the <i>S. aureus</i> 1199 strain, resulted in increase the MIC. In addition, when HDZPNB was associated with ethidium bromide (EB), it caused an increase in the MIC value, thus not inhibiting the efflux pump. For the strain of <i>S. aureus</i> 1199B, carrying the NorA pump, the HDZPNB associated with norfloxacin showed no modulatory, and when the chalcone was used in association with EB, it had no inhibitory effect on the efflux pump. For the tested strain of <i>S. aureus</i> K2068, which carries the MepA pump, it can be observed that the chalcone together the antibiotic resulted in an increase the MIC. On the other hand, when chalcone was used in association with EB, it caused a decrease in bromide MIC, equal to the reduction caused by standard inhibitors. Thus, these results indicate that the HDZPNB could also act as an inhibitor of the <i>S. aureus</i> gene overexpressing pump MepA. The molecular docking reveals that chalcone has a good binding energies −7.9 for HDZPNB/MepA complexes, molecular dynamics simulations showed that Chalcone/MetA complexes showed good stability of the structure in an aqueous solution, and ADMET study showed that the chalcone has a good oral bioavailability, high passive permeability, low risk of efflux, low clearance rate and low toxic risk by ingestion. The microbiological tests show that the chalcone can be used as a possible inhibitor of the Mep A efflux pump. Communicated by Ramaswamy H. Sarma