| Autor: |
Souza MA; Graduate Program in Biological Chemistry, Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil., Rodrigues LG; Science and Technology Centre, Course of Chemistry, State University Vale do Acaraú, Sobral, CE, Brazil., Rocha JE; Graduate Program in Biological Chemistry, Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil., de Freitas TS; Graduate Program in Biological Chemistry, Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil., Bandeira PN; Science and Technology Centre, Course of Chemistry, State University Vale do Acaraú, Sobral, CE, Brazil., Marinho MM; Science and Technology Centre, Course of Chemistry, State University Vale do Acaraú, Sobral, CE, Brazil., Nunes da Rocha M; Graduate Program in Natural Science, State University of Ceará, Fortaleza, CE, Brazil., Marinho ES; Graduate Program in Natural Science, State University of Ceará, Fortaleza, CE, Brazil., Honorato Barreto AC; Department of Physics, Federal University of Ceará, Fortaleza, CE, Brazil., Coutinho HDM; Graduate Program in Biological Chemistry, Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil., Silva LMA; Multiusuary Laboratory of Natural Products Chemistry, Embrapa Tropical Agroindustry, Fortaleza, CE, Brazil., Julião MSDS; Science and Technology Centre, Course of Chemistry, State University Vale do Acaraú, Sobral, CE, Brazil.; Graduate Program in Natural Science, State University of Ceará, Fortaleza, CE, Brazil., Marques Canuto K; Multiusuary Laboratory of Natural Products Chemistry, Embrapa Tropical Agroindustry, Fortaleza, CE, Brazil., Marques da Fonseca A; Academic Master's Degree in Sociobiodiversity and Sustainable Technologies - MASTS, Institute of Engineering and Development Sustainable, University of International Integration of Afro-Brazilian Lusofonia, Acarape, CE, Brazil., Teixeira AMR; Graduate Program in Biological Chemistry, Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil.; Graduate Program in Natural Science, State University of Ceará, Fortaleza, CE, Brazil., Dos Santos HS; Graduate Program in Biological Chemistry, Department of Biological Chemistry, Regional University of Cariri, Crato, CE, Brazil.; Science and Technology Centre, Course of Chemistry, State University Vale do Acaraú, Sobral, CE, Brazil.; Graduate Program in Natural Science, State University of Ceará, Fortaleza, CE, Brazil. |
| Abstrakt: |
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 ( E )-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 S. aureus multi-resistant strains. The modulating effect of HDZPNB chalcone in association with the antibiotic norfloxacin, on the resistance of the S. aureus 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 S. aureus 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 S. aureus 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 S. aureus 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. |
