Structural characterization, DFT calculations, ADMET studies, antibiotic potentiating activity, evaluation of efflux pump inhibition and molecular docking of chalcone (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(4-methoxyphenyl)prop-2-en-1-one

• Published in: Journal of molecular structure 2021-03, Vol.1227, p.129692, Article 129692
• Main Authors: da Cunha Xavier, Jayze, Almeida-Neto, Francisco Wagner de Queiroz, da Silva, Priscila Teixeira, de Sousa, Amanda Pereira, Marinho, Emmanuel Silva, Marinho, Márcia Machado, Rocha, Janaina Esmeraldo, Freitas, Priscila Ramos, de Araújo, Ana Carolina Justino, Freitas, Thiago Santiago, Nogueira, Carlos Emídio Sampaio, de Lima-Neto, Pedro, Bandeira, Paulo Nogueira, Teixeira, Alexandre Magno Rodrigues, Coutinho, Henrique Douglas Melo, dos Santos, Hélcio Silva
• Format: Article
• Language: English
• Subjects: ATR-FTIR; Chalcone; Efflux pump; Fukui; Uv-vis
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2020.129692

•A chalcone was synthesized by Claisen-Schmidt condensation reaction.•Structural, electronic and reactivity properties were obtained using DFT.•ADMET studies were made.•Antimicrobial activities assays were done.•Molecular docking studies were carried out. Chalcones are open-chain flavonoids characterized by two aromatic rings joined by a three-carbon α,β-unsaturated carbonyl system. Over the last several years, chalcones have instigated the interest of chemical and pharmacological researchers due to their simple chemical structure and varied biological activities. Here, we performed the electronic properties, of the chalcone, (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(4-methoxyphenyl) prop-2-en-1-one synthesized by Claisen-Schmidt condensation reaction. The density functional theory method was used with the B3LYP/6-311++G(d,p) level of theory to compute the structural, electronic, and reactivity properties of the chalcone. In addition, microbiological tests were performed to investigate the modulator potential and efflux pump inhibition on Staphylococcus aureus multi-resistant strains. The spectroscopic data analyses allowed drawing the molecular structure of the chalcone synthetized with subsequent confirmation using the quantum chemical calculations. The addition of chalcone to the growth medium caused a synergic effect by reduction of the minimum inhibitory concentration (MIC) values for ciprofloxacin strain. Docking results showed that the chalcone docks in almost the same way as the antibiotic against a MepA model. Druglikeness criteria based on the rules of Lipinski and Veber evaluated that the chalcone has the ideal physicochemical and pharmacokinetic properties to be a good candidate for drug orally. The results confirm the structure of the synthesized chalcone and revealing that the compound can be used as a possible inhibitor of the Mep A efflux pump. [Display omitted]