Vol. 7, Issue 2, Part A (2025)

The emergence of multidrug-resistant bacteria has created an urgent need for new antimicrobial agents. In this work, we report the design, synthesis, and antibacterial evaluation of four novel chalcone-aminoalkyl hybrid compounds. A molecular hybridization strategy was employed to combine the chalcone scaffold (1, 3-diphenyl-2-propen-1-one) with aminoalkyl moieties known for membrane-targeting antibacterial activity. The target compounds were synthesized via Claisen-Schmidt condensation to form chalcone intermediates. All four hybrids were obtained in good yields (80-95%) and fully characterized by IR, NMR, and MS, confirming the expected structures. In vitro antibacterial activity was assessed against Gram-positive (Staphylococcus aureus, Bacillus subtilis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria using a broth microdilution method. The chalcone-aminoalkyl hybrids exhibited significant antibacterial effects, with minimum inhibitory concentrations (MICs) in the low micromolar (4-16 μg/mL) range. Notably, the most potent compound showed MIC values of 2 μg/mL against S. aureus and B. subtilis, and 8 μg/mL against E. coli. These results represent a substantial improvement over simple chalcones (which typically showed MIC ≈ 500 μg/mL) and approach the potency of standard ciprofloxacin (MIC ~0.5-1 μg/mL). Our work illustrates the synthetic scheme and the biologically active chalcone and aminoalkyl pharmacophores and the hybridization concept. In summary, incorporating cationic aminoalkyl groups into the chalcone framework yielded hybrids with enhanced and broad-spectrum antibacterial activity. This study demonstrates the effectiveness of molecular hybridization in antibiotic lead development and provides promising scaffolds for further optimization against resistant infections.