Repurposing the anti-breast cancer drug Tamoxifen: antibacterial and antibiofilm efficacy of novel Tamoxifen-AgNP conjugate against multidrug-resistant healthcare-associated pathogens

Aim: Healthcare-associated infections (HAIs), especially when multidrug-resistant bacteria cause them, pose serious challenges resulting in higher healthcare expenses, increased morbidity, and higher mortality, and thus, there is a need for new antimicrobial agents. Repurposing an old drug for new applications is an important trend, and in the present study, an anti-breast cancer drug, Tamoxifen, has been screened alone and in combination with silver nanoparticles (AgNPs) synthesized using Abutilon indicum Linn. against Enterococcus faecalis, Escherichia coli, and Staphylococcus aureus, which are involved in HAIs. Methods: The drug and the combination were subjected to antimicrobial potential analysis and the determination of minimum inhibitory concentrations (MICs) by agar diffusion and microdilution methods. Biofilm formation assays were performed using the crystal violet method to understand biofilm prevention and eradication efficiencies. The synergism in the activities of the drug and the combination with selected antibiotics was studied using checkerboard assay, and the cytotoxic effects of the drug and the combination on L₉₂₉ cells were analyzed using MTT assay. Results: Tamoxifen and the AgNPs showed promising antibacterial activities, and the MICs of the drug were found to be 62.5 µg/mL (E. coli), 31 µg/mL (S. aureus), and 125 µg/mL (E. faecalis). When combined with AgNPs, Tamoxifen showed a 4-fold reduction in the MIC. The drug also displayed promising antibiofilm activities as it reduced mature S. aureus biofilms by 91%, E. faecalis biofilms by 88%, and E. coli biofilms by 73%. AgNPs alone reduced 91%, 91%, and 81% of biofilms by S. aureus, E. faecalis, and E. coli, respectively, and the combination treatment revealed 92% of S. aureus, 94% of E. faecalis, and 82% of E. coli biofilm eradication at their MICs. Tamoxifen also showed synergism when combined with antibiotics—ampicillin and rifampicin and the AgNPs in combination with Tamoxifen revealed no cytotoxic effect on L₉₂₉ cells at their MICs. Conclusions: All the mentioned studies suggest that Tamoxifen alone and in combination with AgNPs has promising antibacterial and anti-biofilm activities, and it can be developed for better treatment options against HAIs as they are safe for eukaryotic cells.