2. Academic Validation
  3. Discovery of quaternary ammonium compounds with broad antibacterial activity and efficacy in S. aureus infection model

Discovery of quaternary ammonium compounds with broad antibacterial activity and efficacy in S. aureus infection model

  • Eur J Med Chem. 2025 Dec 20:305:118491. doi: 10.1016/j.ejmech.2025.118491.
Akash Shinde 1,  Deepanshi Saxena 2,  Rahul Maitra 2,  Swechchha Singh 3,  Abdul Akhir 2,  Shivani Maykalwar 1,  Kranthi Gupta 4,  B Angayarkanni 5,  Karnati Sai Pranathi 6,  Sunil Misra 7,  Vijayan N Azger Dusthackeer 5,  Jagadeesh Babu Nanubolu 8,  Sidharth Chopra 3,  Haridas B Rode 9
Affiliations

Affiliations

  • 1 Department of Natural Products and Medicinal Chemistry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India.
  • 2 Department of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Sitapur Road, Jankipuram Extension, Lucknow, 226 031, Uttar Pradesh, India.
  • 3 Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India; Department of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Sitapur Road, Jankipuram Extension, Lucknow, 226 031, Uttar Pradesh, India.
  • 4 Department of Natural Products and Medicinal Chemistry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 007, India.
  • 5 Department of Bacteriology, National Institute for Research in Tuberculosis, Chennai, 600 031, India.
  • 6 Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 007, India.
  • 7 Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India; Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 007, India.
  • 8 Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India; Centre for X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
  • 9 Department of Natural Products and Medicinal Chemistry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 007, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201 002, India. Electronic address: haridas.rode@iict.res.in.
PMID: 41500164 DOI: 10.1016/j.ejmech.2025.118491
Abstract

Antimicrobial resistance (AMR) has become a significant global health concern, contributing heavily to the morbidity and mortality associated with both hospital-acquired (nosocomial) and community-acquired infections. In this context, we investigated the Antibacterial potential of quinoline-based quaternary ammonium compounds (QACs) against Gram-positive bacteria, including multidrug-resistant (MDR) strains. Compound 20 was identified through a detail Structure-Activity-Relationship study and demonstrated strong Antibacterial potential with an MIC of 0.125 μg/mL against S. aureus. This compound is effective against clinical MDR-MRSA and VRSA. Of note, 20 effectively inhibited Bacterial growth in both planktonic and biofilm forms in a concentration-dependent manner. It's favorable toxicity profile (SI 72 w.r.t. CHO-K1 cells, HC50 of >100 μg/mL against human RBC) and prolonged post-antibiotic effect (PAE) compared to vancomycin highlights its potency as a safe therapeutic agent. Notably, the compound's in vitro efficacy was successfully translated in vivo, supporting its potential for development into a novel treatment for drug-resistant S. aureus infections, particularly for topical applications.

Keywords

Antibacterial agents; Biofilm inhibitors; Drug resistant S. aureus; Quaternary ammonium compounds; Quinolinium analogues.

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