Efficient Synthesis, Structural Characterization, and Biological Evaluation of Novel Spiro‐oxindole Derivatives via Domino Multicomponent Cycloaddition

Abstract

Spiro‐oxindole frameworks are privileged scaffolds in medicinal chemistry with significant bioactive potential. In this study, two novel spiro‐oxindole derivatives ( 7a and 7b ) were synthesized via an efficient one‐pot domino 1,3‐dipolar cycloaddition. Biological evaluation revealed targeted antibacterial activity against Pseudomonas aeruginosa and Klebsiella pneumoniae (MIC: 100–125 µg/mL), alongside significant antioxidant efficacy in DPPH assays. To rationalize these experimental results, density functional theory (DFT) and molecular electrostatic potential (MEP) mapping were utilized to elucidate key electronic parameters and reactive regions. Additionally, molecular docking simulations identified favorable theoretical binding interactions within bacterial protein targets. To further validate these static docking results, molecular dynamics (MD) simulations confirmed the thermodynamic stability and conformational dynamics of the protein–ligand complexes over time, as characterized by stable RMSD, RMSF, and radius of gyration profiles, alongside sustained key hydrogen‐bond interactions. Ultimately, the correlation between these assays and computational models suggests a plausible mode of action, validating this novel scaffold as a promising framework for the development of dual‐action therapeutic agents.