Exploiting Metal–Ligand Coordination Compounds against Multidrug-Resistant Bacterial Infections by Inhibiting Microbial Growth and Disrupting Biofilm Formation

Development of effective antibacterial strategies with a mechanism of action different from those of prevailing antibiotics remains a critical global challenge, particularly because of the increasing issues of drug resistance. In fact, the formation of bacterial biofilms significantly enhances multidrug resistance (MDR), impedes host immune response, and hinders phagocytosis, leading to persistent chronic infections. In this research, a series of metal–organic coordination compounds, namely, [Mn(adpa)(H 2 O) 2 ] ( 1 ), [Cu(adpa)(H 2 O) 2 ] ( 2 ), and [Zn(adpa)(H 2 O) 2 ] ( 3 ) (H 2 adpa = 3,3 ’ -((anthracen-9-ylmethyl)-azanediyl)-dipropionic acid), were strategically designed, synthesized, and tested against the MDR Gram-positive bacterial strain Staphylococcus aureus, showing promising antibacterial and antibiofilm activities. The composition and integrity of compound frameworks ( 1–3 ) were established by UV–vis and fluorescence titrations, microanalysis, and molar conductivity. Density functional theory (DFT) computation using the B3LYP/6–311G level of theory was applied to ascertain the molecular structures of 1–3, suggesting a distorted square pyramidal geometry around the metal centers. As established by multiple bioassays, 1–3 showed excellent antibacterial activity against the MDR strain of a clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA CI) with minimum inhibitory concentration (MIC) values of 500, 350, and 250 μg/mL, respectively. The antibiofilm assay indicated that 1–3 possessed enhanced antibiofilm potency against MRSA CI with biofilm inhibition values of 66.03, 70.94, and 75.47%, respectively. The antivirulence nature of 1–3, as observed from different biological experiments, revealed that they had the ability to disarm the MRSA CI pathogens by blocking several virulence factors, thereby targeting a specific pathogenic mechanism and preventing the infection. However, compound 3 displayed superior antimicrobial activity in comparison to compounds 1 and 2 . This work delineated that appropriately designed metal compounds have a potential role in the quest for antimicrobials in defense against bacteria in the era of current antimicrobial resistance.