Rhenium tricarbonyl complexes of thiazolohydrazinylidene-chroman-2,4-diones derivatives: antibacterial activity and in vivo efficacy.

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 currently evaluated for the possible development of alternative antimicrobial agents. 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 (zebrafish-S. aureus ATCC43300 model of infection), efficiently eradicating Methicillin-resistant Staphylococcus aureus (MRSA) infection at doses of 500 and 520 ng/mL respectively. In vitro studies indicate that, contrary to other known active rhenium complexes, the compounds do not affect peptidoglycan synthesis or compromise the integrity of the cytoplasmic membrane, but rather that bacterial membrane depolarization may play a role in their antibiotic activity.