Novel nano-catalytic strategy for selective imine-chalcone hybrid functionalization: synthesizing, bioactivity evaluations, molecular docking, ADME, DFT, and SAR analysis.

In the present study, plant-mediated copper nanoparticles (Cu NPs) were employed as a heterogenous nano-catalyst for the synthesis of imine-chalcone hybrids via C(sp3)H functionalization of Schiff base precursor with aromatic aldehydes. The transformation proceeded under mild conditions. The catalytic role of copper nanoparticles is proposed to involve coordination-assisted activation of the imine substrate, facilitating selective products formation. Seven imine-chalcone derivatives (5a-e, 7, and 9) were synthesized and characterized by spectroscopic techniques. The compounds were tested for antimicrobial activity against different bacterial and fungal strains, revealing moderate to promising inhibitory effects depending on their substituent patterns. The results showed that, 4-fluoro substituent (5b) exhibited strongest antibacterial activity (zone of inhibition for Escherichia coli, 40 mm and Staphylococcus aureus, 36 mm) in comparison to the other products. Whereas, 4-hydroxy substituent (5d), was highly effective to inhibit the growth of Candida albicans with 37 mm. The products were also evaluated for their antioxidant activity, demonstrating that the product (5a) recorded strongest radical scavenging activity (IC50 = 0.359 μg/mL) near to standard ascorbic acid (IC50 = 0.330 μg/mL). Molecular docking of the products was performed and supported the biological activity and interaction with microbial proteins, also the products were analyzed for ADME prediction. Density functional theory (DFT) analysis calculations were conducted to display the energy gap, electron density, and quantum chemical parameters of the products (5a-e). While the mechanistic aspects require further experimental validations, the study highlights the potential of plant-derived CuNPs catalytic role for construction of biologically efficient hybrid scaffolds.