ArticleMicrobial biotechnology2025
Multi-Halogenated Indoles as Antimicrobial and Antivirulence Agents Against Drug-Resistant Staphylococcus aureus.
Article in Microbial biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Nematicidal activity of multi-halogenated indoles against Caenorhabditis elegans.Pest management science · 2026Article
- Structure-Activity Relationships of Hemocompatible Cationic 6-Azaindole Pyridinium Salts: Antimicrobial and Anticancer Activity.Molecules (Basel, Switzerland) · 2026Article
- Halogenated indoles selectively modulate plant growth and root development.Frontiers in plant science · 2026Article
- Multi-Halogenated Indoles as Antimicrobial and Antivirulence Agents Against Drug-Resistant Staphylococcus aureus.Microbial biotechnology · 2025Article
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Authors and funding
5 authors.
Funding
Abstract
The emergence of multidrug-resistant Staphylococcus aureus requires the development of novel agents that can target both planktonic cells and persistent biofilms. In this study, a library of multi-halogenated indoles was evaluated for antibacterial, antibiofilm and antivirulence activities against S. aureus including methicillin-resistant strains. Two lead compounds, 6-bromo-4-iodoindole and 4-bromo-6-chloroindole, exhibited potent bactericidal activity (MIC = 20-30 μg/mL) comparable to the antibiotic gentamicin, effectively inhibited biofilm formation and persister formation and suppressed key virulence haemolysis. These effects were associated with intracellular ROS generation and transcriptional downregulation of quorum-sensing genes of agrA and RNAIII and virulence genes of hla and nuc1. Also, 6-bromo-4-iodoindole synergised with aminoglycoside tobramycin and gentamicin, significantly reducing their effective MICs. Notably, these two multi-halogenated indoles did not induce drug resistance for 20 days while gentamicin rapidly increased drug resistance. Cytotoxicity assays in HepG2 cells and phytotoxicity tests confirmed a favourable safety profile. Structure-activity relationship identified multi-halogenation at the C4, C5, C6 and C7 positions of indole as favourable for enhanced activities and also suggested that more halogens could improve the activities. This study highlights multi-halogenated indoles as promising multi-target antimicrobial agents with potential therapeutic and environmental applications against S. aureus, including drug-resistant and biofilm-forming strains.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.