Microwave-assisted synthesis of poly aromatic pyrimido[4,5-b]quinoline derivatives: Design, in silico pharmacokinetics, molecular dynamics simulation, molecular docking, POM analysis, and in vitro antimicrobial screening

A series of polyaromatic Pyrimido[4,5-b]quinoline derivatives 4(a–j) were synthesized using a rapid and efficient microwave-assisted method. The targeted Compounds 4(a–j) showed significant antibacterial and antifungal activity. Structural design was guided by rational drug design principles to enhance antimicrobial potential. The synthesized compounds were subjected to comprehensive in silico pharmacokinetic profiling (ADMET) to predict drug-likeness and bioavailability. Molecular docking studies were performed to assess binding interactions with key microbial targets, followed by molecular dynamics (MD) simulations to evaluate the stability of ligand–target complexes. POM (Petra/Osiris/Molinspiration) analysis further supported the biological relevance of the compounds. In vitro antimicrobial screening against selected bacterial and fungal strains revealed promising activity, with some derivatives demonstrating superior potency compared to standard drugs. The integration of green synthesis, computational modeling, and biological validation highlights these compounds as potential scaffolds for future antimicrobial drug development. Docking studies with S. aureus NDK (PDB ID: 3Q89) revealed strong molecular interactions. ADME, Lipinski, and Veber analyses predicted good bioavailability and safety. Molecular dynamics confirmed stability, highlighting this method's promise in green medicinal chemistry.Structural elucidation of the synthesized compounds was confirmed through FT-IR, ¹H NMR, ¹³C NMR, and ESI mass spectrometry