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Spectroscopic analysis by NMR, FT-Raman, ATR-FTIR, and UV-Vis, evaluation of antimicrobial activity, and in silico studies of chalcones derived from 2-hydroxyacetophenone

2021; Elsevier BV; Volume: 1241; Linguagem: Inglês

10.1016/j.molstruc.2021.130647

1872-8014

Jayze da Cunha Xavier, Francisco Wagner Queiroz Almeida-Neto, Janaína Esmeraldo Rocha, Thiago Sampaio de Freitas, Priscila Ramos Freitas, Ana Carolina Justino de Araújo, Priscila T. da Silva, C.E.S. Nogueira, Paulo Nogueira Bandeira, Márcia Machado Marinho, Emmanuel Silva Marinho, Nitin Kumar, Antônio C.H. Barreto, Henrique Douglas Melo Coutinho, Murilo Sérgio da Silva Julião, Hélcio Silva dos Santos, Alexandre Magno Rodrigues Teixeira,

Synthesis and Characterization of Heterocyclic Compounds

Six 2’-hydroxychalcones were synthesized and characterized by NMR, FT-Raman, ATR-FTIR, and UV-Vis. These chalcones alone and in combination with the ciprofloxacin, penicillin, and erythromycin antibiotics were tested against multiresistant strains of Staphylococcus aureus. It was also verified by in vitro and in silico studeis the capacity of these chalcones to inhibit the NorA efflux pump. The MICs values of ciprofloxacin were reduced in the presence of all tested chalcones. For norfloxacin antibiotic, the chalcones A1, A4, A5 and A6 promoted the reduced in the MIC values. The A2 chalcone was the only one to reduce the MIC values when associated with penicillin. Any chalcones were not able to reduce MIC values when associated with erythromycin. These results indicate that the synergistic effects demonstrated for the synthesized chalcones were influenced by the introduction of a furanic ring (A1), a chlorine atom and a methoxy group at the C4 position (A2 and A4), a second double bond (A5), and a fluorine atom at the C2 position (A6). The ADMET analysis predicts that the chalcones A2, A3, A5 and A6 have easier cell permeation. The nucleophilic region makes the A5 chalcone capable of covalently bonding with plasma proteins, and the presence of oxygenated aromatic substitutions makes the chalcones A1 and A4 more water-soluble and consequently easier to excrete. On the other hand, the substitution of the methoxy group of the A4 chalcone makes it more susceptible to O-demethylation reactions by the CYP3A4 isoenzyme. The molecular docking revealed that all six chalcones could hinder the binding of norfloxacin to the NorA efflux pump.