Journal Article Epublish
PubMed: 42883957 DOI: 10.3390/ijms27198713
Adjuvant Effect of Meldrum's Acid Derivatives on Antibiotic Activity Against Multidrug-Resistant Bacteria.
Int J Mol Sci 27(19)
Authors: Isaac Moura Araújo, Ewerton Yago de Sousa Rodrigues, Daniel Sampaio Alves, Clara Mariana Gonçalves Lima, Sheila Alves Gonçalves, Cícera Georgia Brito Milfont, Alisson Justino Alves da Silva, João Arthur de Oliveira Borges, Cícera Datiane de Morais Oliveira-Tintino, Samara Alves Brito, José Thyálisson da Costa Silva, Francisco Assis Bezerra da Cunha, Ricardo Andrade Rebelo, Iêda Maria Begnini, Renata Salamoni, Luiz Everson da Silva, Nathalia Monteiro Lins Freire, Renata Ferreira Santana, Thiago Mendonça de Aquino, Saulo Relison Tintino, Henrique Douglas Melo Coutinho
Affiliations
- Department of Biological Chemistry, Regional University of Cariri-URCA, Crato 63105-000, Ceará, Brazil.
- Department of Chemistry, Regional University of Blumenau, FURB, Blumenau 89030-903, Santa Catarina, Brazil.
- Department of Chemistry, Federal University of Paraná, UFPR, Curitiba 81531-970, Paraná, Brazil.
- Institute of Chemistry and Biotechnology, Federal University of Alagoas, UFAL, Maceió 57072-970, Alagoas, Brazil.
- Department of Nutrition, Federal University of Tocantins, Palmas 77001-090, Tocantins, Brazil.
Abstract
Antimicrobial resistance demands new strategies capable of restoring the effectiveness of conventional antibiotics. In this study, the antibacterial activity and adjuvant potential of five Meldrum's acid derivatives (MAD1-MAD5) against multidrug-resistant strains of Staphylococcus aureus 10 and Escherichia coli 06 were evaluated. Minimum inhibitory concentrations (MICs) were determined by broth microdilution, and the combined effects with ampicillin, gentamicin, and norfloxacin were analyzed at subinhibitory concentrations. Membrane permeability was assessed by SYTOX Green fluorescence, and bacterial energy metabolism was assessed by quantifying intracellular ATP using bioluminescence. The derivatives did not show direct antibacterial activity (MIC ≥ 1024 µg/mL), but they significantly reduced the MICs of the antibiotics, especially gentamicin and norfloxacin. Increased membrane permeability and reduced ATP levels were most evident in E. coli, particularly for MAD3, MAD4, and MAD5, while S. aureus showed a limited response. In silico ADMET predictions indicated pharmacokinetic profiles consistent with bioactive compounds. Taken together, the results demonstrate that Meldrum's acid derivatives act as species-dependent modulators of antimicrobial resistance, highlighting their potential as antibacterial adjuvants.
MeSH
Norfloxacin, Escherichia Coli, Bacteria