ArticleChemical science2023
Small molecular adjuvants repurpose antibiotics towards Gram-negative bacterial infections and multispecies bacterial biofilms.
Article in Chemical science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
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- Synthesis of carbazole and naphthyl-pyrimidine-based inhibitors of Xanthomonas for tomato bacterial spot management.Molecular diversity · 2026Article
- Review
- Dicarboxylate and dicarboxylic acid appended supramolecular self-associating amphiphiles as antimicrobial agents against high priority bacterial pathogens.Organic & biomolecular chemistry · 2025Article
- Development of a nitric oxide-releasing cephalexin-based hybrid compound for enhanced antimicrobial efficacy and biofilm disruption.RSC medicinal chemistry · 2025Article
- Drug Repurposing: An Emerging Strategy inJournal of microbiology and biotechnology · 2025Review
- Protein-based nanoparticles for antimicrobial and cancer therapy: implications for public health.RSC advances · 2025Review
- Article
- Potential Use of Selected Natural Compounds with Anti-Biofilm Activity.International journal of molecular sciences · 2025Review
- Antimicrobial Impact of Wood Vinegar Produced Through Co-Pyrolysis of Eucalyptus Wood and Aromatic Herbs.Antibiotics (Basel, Switzerland) · 2024Article
- Pyrrolidine-2,3-diones: heterocyclic scaffolds that inhibit and eradicateChemical communications (Cambridge, England) · 2024Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gram-negative bacterial infections pose a significant challenge due to two major resistance elements, including the impermeability of the outer membrane and the overexpression of efflux pumps, which contribute to antibiotic resistance. Additionally, the coexistence of multispecies superbugs in mixed species biofilms further complicates treatment, as these infections are refractory to most antibiotics. To address this issue, combining obsolete antibiotics with non-antibiotic adjuvants that target bacterial membranes has shown promise in combating antibacterial resistance. However, the clinical translation of this cocktail therapy has been hindered by the toxicity associated with these membrane active adjuvants, mainly due to a limited understanding of their structure and mechanism of action. Towards this goal, herein, we have designed a small molecular adjuvant by tuning different structural parameters, such as the balance between hydrophilic and hydrophobic groups, spatial positioning of hydrophobicity and hydrogen bonding interactions, causing moderate membrane perturbation in bacterial cells without any toxicity to mammalian cells. Moderate membrane perturbation not only enhances the internalization of antibiotics, but also increases the intracellular concentration of drugs by hampering the efflux machinery. This revitalises the efficacy of various classes of antibiotics by 32-512 fold, without inducing toxicity. The leading combination not only exhibits potent bactericidal activity against
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Registered trials
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