Rhenium tricarbonyl coumarin complexes as promising anti-MRSA candidates targeting bacterial biofilms and systemic infection, with reduced resistance development

Abstract

Antimicrobial resistance (AMR) is a major threat to public health, causing serious issues in the successful prevention and treatment of persistent diseases. Transition metal complexes are being intensively researched as promising alternatives to traditional antibiotics for the development of novel antimicrobial therapies. In our ongoing efforts to identify safe and effective rhenium-based antibiotics, we have prepared a family of compounds bearing derivatives of thiazolohydrazinylidene-chroman-2,4-diones. Two compounds were identified as being active and nontoxic in vivo in the zebrafish infection model, efficiently eradicating methicillin-resistant Staphylococcus aureus (MRSA) infection at doses of ca. 500 ng mL−1. Most importantly, our data show for the first time that MRSA did not develop resistance to this class compounds, while one of the identified molecules effectively disintegrated already formed mature MRSA biofilm.