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

Abstract

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.

Graphical Abstract

Keywords:

• 1,2,3-Triazole
• chalcone
• morpholine
• antibacterial activity
• ADMET predictions

Acknowledgment

FK and ACG thank MHRD for providing fellowship. JB is thankful to the Director, National Institute of Technology Calicut for providing research facilities and Faculty Research Seed Grant (FRG) to carry out this work. RG thanks the Director, ICMR-NIREH, Bhopal for scientific support. All authors are thankful to CMC, NIT Calicut for the characterization of data, and Dr. Ranjith Kumavath, the Central University of Kerala for anticancer activity studies.

Disclosure statement

No potential conflict of interest was reported by the author(s).