Vol. 7, Issue 9, Part A (2025)

The persistent rise in antimicrobial resistance and the growing burden of chemo-resistant breast cancer have driven the need for dual-acting therapeutic agents. In this study, four novel Mannich base derivatives (N₁-N₄) were synthesized via a classical one-pot condensation of 4-ethoxyacetophenone with different substituted secondary amines. The structures were confirmed through FTIR, ¹H-NMR, and ¹³C-NMR spectral analysis. Antibacterial activity was evaluated using the agar well diffusion method against Staphylococcus aureus and Escherichia coli, while cytotoxicity against the MCF-7 breast cancer cell line was assessed using the MTT assay. Notably, compounds N₂ and N₃ demonstrated moderate to strong antibacterial activity, with N₂ showing 20 mm and 18 mm inhibition zones against S. aureus and E. coli, while N₃ recorded 16 mm and 14 mm, respectively, at 0.1 mg/mL. In contrast, N₁ and N₄ exhibited potent cytotoxic effects, with IC₅₀ values of 18.7 µg/mL and 21.3 µg/mL, respectively. Furthermore, molecular docking of N₁ with the estrogen receptor alpha (PDB: 5T92) revealed stable binding with a docking affinity of -7.73 kcal/mol, supported by favorable hydrogen bonding and hydrophobic interactions with MET421 and PHE404. These results suggest that specific substitutions on the amine moiety significantly influence biological activity, either through enhanced cellular uptake or better receptor binding. Overall, this study confirms that structural tuning of Mannich bases can yield promising multifunctional compounds, potentially overcoming the limitations of single-target therapies. Future research may further optimize these derivatives for selectivity, bioavailability, and in vivo efficacy.