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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 through Claisen–Schmidt
condensation to form chalcone intermediates. All four hybrids were
obtained in good yields (80–95%) and fully characterized by
infrared, nuclear magnetic resonance, and MS, confirming the
expected structures. In vitro, antibacterial activity was assessed
against Gram-positive (Staphylococcus aureus and Bacillus subtilis)
and Gram-negative (Escherichia coli and 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, 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. |
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Key words: Aminoalkyl substituent,
Antibacterial activity, Chalcone hybrid, Medicinal chemistry,
Molecular hybridization. |
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Indian Journal of Advances in Chemical Science,
Volume: 13, Issue : 2, January 2025
ISSN No.: 2320-0898 (Print);
2320-0928 (Electronic) |
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