Antibacterial and Anti-Breast Cancer Activities of Novel Imine-Amoxicillin Derivatives: In Vitro and In Silico Investigations

Background Antibiotic resistance poses a growing global health challenge, prompting the scientific community to explore novel strategies, including drug repurposing. Amoxicillin, a widely used β-lactam antibiotic, has recently shown potential for modification into compounds with extended bioactivity. Objectives The chemical modification of amoxicillin has expanded its therapeutic scope, suggesting that structurally engineered antibiotics may serve as promising candidates in both microbiology and oncology. Methodology: In this study, two imine derivatives of amoxicillin, designated A and B, were synthesized via condensation with substituted benzaldehydes in glacial acetic acid. The antibacterial efficacy of synthesized derivatives against four pathogens ( E. coli, Streptococcus pneumoniae, Bacillus subtilis , and Staphylococcus spp .). At the same time, the cytotoxic effects were assessed on the breast cancer cell line MCF-7. Results Derivative A consistently exhibited higher antibacterial activity than amoxicillin, with inhibition zones reaching 34 mm against E. coli and 27 mm against B. subtilis. Regarding its anticancer properties, derivative A exhibited concentration-dependent inhibition of MCF-7 cell viability, achieving a 93.4% reduction at 360 ppm and an IC₅₀ of approximately 118.14 ppm. Additionally, molecular docking revealed strong binding affinity between derivative A and the estrogen receptor (PDB: 3PP0), primarily via hydrogen bonding and hydrophobic interactions. Discussion ADME analysis further confirmed the drug-likeness of the compound, with acceptable pharmacokinetic parameters; however, oral bioavailability may be limited by its high molecular weight and low gastrointestinal absorption. If these imine derivatives are optimized for better solubility and delivery, they may offer dual-function therapeutic agents.