Antibacterial and molecular docking studies with protein stability studies into dihydropyrimidinones synthesized via...

This study reports the green synthesis of eco-friendly silver nanoparticles (AgNPs) using Aloe vera gel extract and their application as an efficient heterogeneous catalyst for the one-pot, three-component Biginelli synthesis of 3,4-dihydropyrimidin-2(1 H)-ones (DHPMs). The biosynthesized AgNPs were thoroughly characterized using UV-Vis, FTIR, XRD, SEM-EDX, and HR-TEM-SAED techniques, confirming crystalline, spherical particles. Catalyst optimization studies revealed that a low catalyst loading of 20 mg at 80 °C yielded maximum product outputs of up to 96% within an optimized reaction time of 1 h. Structural elucidation of the synthesized DHPM derivatives was completed using FTIR, ¹H NMR, ¹³C NMR, and mass spectrometry (MS). Biological screening demonstrated that the derivatives possessed significant antibacterial activity, with compound 4e exhibiting a prominent zone of inhibition (17 mm) against Salmonella typhimurium (MTCC 98). To decode the underlying mechanism, Prediction of Activity Spectra for Substances (PASS) analysis was paired with molecular docking against the Gluconate 2-dehydrogenase receptor (PDB ID: 5GNA). The PASS analysis reveals that the synthesized compounds display considerable activity as both an antieczematic agent and a Gluconate 2-dehydrogenase (acceptor) inhibitor, with a probability value (Pa) exceeding 0.07. Compound 4e demonstrated excellent binding affinity with a docking score of -8.2 kcal/mol. Furthermore, Normal Mode Analysis (NMA)-based Molecular Dynamics (MD) simulations verified the long-term stability of the protein-ligand complex, showing low main-chain deformability and a rigid eigenvalue of 4.18 × 10^- 4. These quantitative results establish this green catalytic path as a highly efficient strategy for producing bioactive heterocycles.