New Chalcone Derivatives: Synthesis, Characterization, Antioxidant, Antimicrobial, and Docking Study Against GLcN-6-P Synthase

Background: Chalcone derivatives are well-known for their versatile pharmacological properties, particularly their antimicrobial and antioxidant activities. Their simple chemical structure and ease of synthesis make them attractive candidates for drug discovery, especially in combating microbial resistance and oxidative stress-related disorders. Objective: The study aimed to synthesize and characterize a series of new chalcone derivatives and evaluate their antimicrobial and antioxidant activities, alongside molecular docking studies to assess their potential as therapeutic agents. Methods: Six new chalcone derivatives were synthesized via Claisen–Schmidt condensation of two methyl ketones (p-aminoacetophenone and cyclopropyl methyl ketone) with p-substitutedphenyl aldehydes under mild conditions. Structural elucidation was performed using FT-IR, 1H-NMR, 13C-NMR, and GC-MS spectroscopy. Antimicrobial activities were tested against five microbial strains: Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, and Candida albicans, using the agar well-diffusion method. Antioxidant activity was evaluated using the standard DPPH radical scavenging assay. Molecular docking studies were conducted using PyRx software to investigate the binding interactions of the synthesized chalcones with the active site of glucosamine-6-phosphate (GlcN-6-P) synthase, a target enzyme for antimicrobial agents. Results: The synthesized chalcone derivatives were successfully characterized and exhibited varying levels of antimicrobial activity against the tested strains, with some compounds demonstrating significant inhibitory effects. Antioxidant assays revealed promising radical scavenging capabilities for several synthesized chalcones. Docking studies showed favorable binding affinities between the identified compounds and the GlcN-6-P synthase active site, supporting the experimental bioactivity results. Conclusions: This study demonstrates that the newly synthesized chalcone derivatives possess both antimicrobial and antioxidant activities. Their effective interaction with GlcN-6-P synthase suggests potential for further development as lead compounds in antimicrobial drug research.