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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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\u2019s acid derivatives (MAD1\u2013MAD5) 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 \u2265 1024 \u00b5g\/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\u2019s acid derivatives act as species-dependent modulators of antimicrobial resistance, highlighting their potential as antibacterial adjuvants.<\/jats:p>","DOI":"10.3390\/ijms27198713","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:14:37Z","timestamp":1790694877000},"page":"8713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adjuvant Effect of Meldrum\u2019s Acid Derivatives on Antibiotic Activity Against Multidrug-Resistant Bacteria"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6544-0141","authenticated-orcid":false,"given":"Isaac Moura","family":"Ara\u00fajo","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, Regional University of Cariri\u2014URCA, Crato 63105-000, Cear\u00e1, 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