Discovery of Ruthenium(Arene) Metalloantibiotics: Advancing Selective and Potent Therapeutics against Gram-Negative Acinetobacter baumannii.

Authors

Kajal Chaudhary, Bhumika Agrahari, Himanshu Sonker, Sayari Dewan, Ritika Gautam Singh

Published in

Journal of medicinal chemistry. Oct 17, 2025. Epub Oct 17, 2025.

Abstract

No new class of antibiotics active against Acinetobacter baumannii─a critical WHO priority pathogen (2024)─has reached clinical use in over 50 years. To address this, we designed, synthesized, and characterized a novel library of ruthenium arene complexes and screened them against various bacterial strains. Antibacterial assays identified Ru5 as a potent lead compound, exhibiting ultralow minimum inhibitory concentrations (MICs) against A. baumannii (MIC = 4 μg/mL) and Staphylococcus aureus (MIC = 0.5 μg/mL), with no resistance emerging after 20 passages. Ru5 also showed strong, selective activity against both planktonic and biofilm-associated bacteria, achieving 78% eradication of A. baumannii and 57% of S. aureus at 20 × MIC. Furthermore, Ru5 effectively disrupted polymicrobial cocultured biofilms. Its therapeutic efficacy was validated in a BALB/c mouse skin abscess model infected with A. baumannii. This new chemical class represents a promising foundation for next-generation broad-spectrum antibiotics targeting invasive infections caused by A. baumannii.

PMID:
41108038
Bibliographic data and abstract were imported from PubMed on 18 Oct 2025.

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