Pharmacokinetic, Antimicrobial, Antibiofilm, and Virulence Target Binding Propensities of a Hetero-Ligated Thiolato-Bridged Dinuclear Metallacyclic Manganese(I)-based CO-Releasing Molecule.

Abstract

Staphylococcus aureus and Escherichia coli remain major concerns in global public health, posing clinical challenges due to their adaptability, virulence, and biofilm-mediated persistence. The continued emergence of drug-resistant strains necessitates the development of new antimicrobial compounds. In this study, we evaluated the multifunctional potential of a hetero-ligated, thiolato-bridged dinuclear metallacyclic Mn(I)-based CO-releasing compound (S-MnC), analysing its antibacterial, antibiofilm, molecular, and target-binding efficacies against S. aureus and E. coli. The antibacterial potential of S-MnC was confirmed by a significant decrease in bacterial growth, biofilm biomass, matrix integrity, motility, and structural integrity. Our results further confirmed its anti-adhesive potential, demonstrating the depletion of intracellular free thiols and an increase in reactive oxygen species. Additionally, S-MnC displayed safe hemolysis levels. ADMET analysis indicated a good balance of drug-likeness properties. Molecular docking studies suggested potential binding sites of S-MnC to molecular targets such as bacterial DNA Gyrase B, SaeR, SaeS, and SarA of S. aureus, as well as DNA Gyrase B and SdiA of E. coli, suggesting the antivirulence mechanisms mediated by S-MnC. In this study, we report, for the first time, the antibacterial and antibiofilm activities of S-MnC against both Gram-negative, E. coli, and Gram-positive, S. aureus, and its binding affinity to multiple molecular and virulence targets.