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Emerging multi-drug resistance (MDR) bacteria are alarming the medicinal chemistry community to establish a new class of antimicrobials with high selectivity, less toxicity, and a new mode of action. Therefore, a new series of chalcone-morpholine hybrids ( 6a–p ) were synthesized using copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition to link the above two pharmacophores with the 1,2,3-triazole ring. Antibacterial potentials of all the synthesized compounds were studied against two Gram-positive ( Bacillus subtilis  and  Staphylococcus aureus ), and three Gram-negative ( Escherichia coli ,  Pseudomonas putida , and  Klebsiella pneumonia ) bacterial strains. Among the tested series of compounds,  6a ,  6c , and  6m  against all the bacterial strains,  6e  against both the Gram-positive bacteria, and  6h  against all the Gram-negative bacteria were found to exhibit broad-spectrum activity compared with the standard Ampicillin. Furthermore,  in silico  ADME profiles were also predicted to set effective lead candidates for effective antibacterial agents.

1,2,3-Triazole Linked Chalcone-Morpholine Hybrids: Synthesis, In Vitro Antibacterial Evaluation and In Silico ADMET Predictions