Adjuvant Effect of Meldrum’s Acid Derivatives on Antibiotic Activity Against Multidrug-Resistant Bacteria
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.
Authors
- Thiago Mendonça de Aquino (ORCID: https://orcid.org/0000-0001-9138-8466)
- Cícera Datiane de Morais Oliveira–Tintino (ORCID: https://orcid.org/0000-0003-1316-7064)
- Cícera Georgia Brito Milfont (ORCID: https://orcid.org/0000-0002-0718-360X)
- Ricardo Andrade Rebelo (ORCID: https://orcid.org/0000-0003-1362-1837)
- João Arthur de Oliveira Borges
- Clara Mariana Gonçalves Lima (ORCID: https://orcid.org/0000-0002-3150-9139)
- José Thyálisson da Costa Silva (ORCID: https://orcid.org/0009-0002-7522-2989)
- Iêda Maria Begnini
- Samara Alves Brito (ORCID: https://orcid.org/0000-0003-0629-7936)
- Luiz Everson da Silva (ORCID: https://orcid.org/0000-0002-2332-3553)
- Henrique Douglas Melo Coutinho (ORCID: https://orcid.org/0000-0002-6634-4207)
- Isaac Moura Araújo (ORCID: https://orcid.org/0000-0002-6544-0141)
- Renata Ferreira Santana (ORCID: https://orcid.org/0000-0001-6621-6662)
- Saulo Relison Tintino (ORCID: https://orcid.org/0000-0002-7733-9331)
- Nathalia Monteiro Lins Freire (ORCID: https://orcid.org/0009-0006-7079-1751)
- Renata Salamoni
- Sheila Alves Gonçalves
- Daniel Sampaio Alves (ORCID: https://orcid.org/0009-0003-5307-5049)
- Francisco Assis Bezerra da Cunha (ORCID: https://orcid.org/0000-0001-9130-0735)
- Alisson Justino Alves da Silva (ORCID: https://orcid.org/0009-0003-5897-2857)
- Ewerton Yago de Sousa Rodrigues (ORCID: https://orcid.org/0000-0001-9395-2008)
Institutions
- Universidade Federal do Tocantins (BR)
- Universidade Regional de Blumenau (BR)
- Universidade Regional do Cariri (BR)
- Universidade Federal do Paraná (BR)
- Universidade Federal de Alagoas (BR)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2026-09-29
- DOI
- https://doi.org/10.3390/ijms27198713
- Primary Topic
- Antimicrobial Peptides and Activities
- Type
- article
- Field-Weighted Citation Impact
- 0.00