Synthesis, spectroscopic characterization, and antibacterial activity of chalcone (2E)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one against multiresistant Staphylococcus aureus carrier of efflux pump mechanisms and β-lactamase.

Autor: da Silva L; Laboratory of Semi-Arid Bioprospecting (LABSEMA), Department of Biological Chemistry, URCA, Crato, Brazil., Donato IA; Laboratory of Semi-Arid Bioprospecting (LABSEMA), Department of Biological Chemistry, URCA, Crato, Brazil., Bezerra SR; Laboratory of Semi-Arid Bioprospecting (LABSEMA), Department of Biological Chemistry, URCA, Crato, Brazil., Dos Santos HS; Chemical Laboratory of Natural and Synthetic Products (LQPN), State University of Ceará (UECE), Fortaleza, Brazil.; Department of Chemistry, Vale do Acaraú State University, Sobral, Brazil.; Postgraduate Program in Natural Sciences - PPGCN, State University of Ceará, Fortaleza, Brazil., Bandeira PN; Chemical Laboratory of Natural and Synthetic Products (LQPN), State University of Ceará (UECE), Fortaleza, Brazil., do Nascimento MTR; Chemical Laboratory of Natural and Synthetic Products (LQPN), State University of Ceará (UECE), Fortaleza, Brazil., Guedes JM; Chemical Laboratory of Natural and Synthetic Products (LQPN), State University of Ceará (UECE), Fortaleza, Brazil., Freitas PR; Laboratory of Microbiology and Molecular Biology (LMBM), Department of Biological Chemistry, URCA, Crato, Brazil., de Araújo ACJ; Laboratory of Microbiology and Molecular Biology (LMBM), Department of Biological Chemistry, URCA, Crato, Brazil., de Freitas TS; Laboratory of Microbiology and Molecular Biology (LMBM), Department of Biological Chemistry, URCA, Crato, Brazil., Coutinho HDM; Laboratory of Microbiology and Molecular Biology (LMBM), Department of Biological Chemistry, URCA, Crato, Brazil., de Matos YMLS; Laboratory of Semi-Arid Bioprospecting (LABSEMA), Department of Biological Chemistry, URCA, Crato, Brazil., de Oliveira LCC; Laboratory of Spectroanalytical, Biological and Environmental Chemistry-LEQBA, URCA, Crato, Brazil., da Cunha FAB; Laboratory of Semi-Arid Bioprospecting (LABSEMA), Department of Biological Chemistry, URCA, Crato, Brazil.; Chemical Laboratory of Natural and Synthetic Products (LQPN), State University of Ceará (UECE), Fortaleza, Brazil.; Department of Chemistry, Vale do Acaraú State University, Sobral, Brazil.; Postgraduate Program in Natural Sciences - PPGCN, State University of Ceará, Fortaleza, Brazil.
Jazyk: angličtina
Zdroj: Fundamental & clinical pharmacology [Fundam Clin Pharmacol] 2024 Feb; Vol. 38 (1), pp. 60-71. Date of Electronic Publication: 2023 Jul 27.
DOI: 10.1111/fcp.12938
Abstrakt: Background: The bacterium Staphylococcus aureus has stood out for presenting a high adaptability, acquiring resistance to multiple drugs. The search for natural or synthetic compounds with antibacterial properties capable of reversing the resistance of S. aureus is the main challenge to be overcome today. Natural products such as chalcones are substances present in the secondary metabolism of plants, presenting important biological activities such as antitumor, antidiabetic, and antimicrobial activity.
Objectives: In this context, the aim of this work was to synthesize the chalcone (2E)-1-(3'-aminophenyl)-3-(4-dimethylaminophenyl)-prop-2-en-1-one with nomenclature CMADMA, confirm its structure by nuclear magnetic resonance (NMR), and evaluate its antibacterial properties.
Methods: The synthesis methodology used was that of Claisen-Schmidt, and spectroscopic characterization was performed by NMR. For microbiological assays, the broth microdilution methodology was adopted in order to analyze the antibacterial potential of chalcones and to analyze their ability to act as a possible inhibitor of β-lactamase and efflux pump resistance mechanisms, present in S. aureus strain K4100.
Results: The results obtained show that CMADMA does not show direct antibacterial activity, expressing a MIC of ≥1024 μg/mL, or on the enzymatic mechanism of β-lactamase; however, when associated with ethidium bromide in efflux pump inhibition assays, CMADMA showed promising activity by reducing the MIC of the bromide from 64 to 32 μg/mL.
Conclusion: We conclude that the chalcone synthesized in this study is a promising substance to combat bacterial resistance, possibly acting in the inhibition of the QacC efflux pump present in S. aureus strain K4100, as evidenced by the reduction in the MIC of ethidium bromide.
(© 2023 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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