Microwave assisted synthesis and antimicrobial evaluation of novel Thiazolidinedione pyrrole hybrids with antiviral potential and comprehensive computational modeling studies

A novel class of N-substituted thiazolidine-2,4-dione/pyrrole-2,5-dione moiety derivatives 3(a–g) was synthesized via C–N bond formation through SN2-mediated reaction, utilizing microwave-assisted synthesis to enhance reaction efficiency and product yield. This approach enabled the rapid and selective formation of the target compounds, which were evaluated for their in vitro antimicrobial activity against a variety of bacterial and fungal strains. The compounds demonstrated promising antibacterial and antifungal properties, with compound 3g showing the highest activity, producing significant inhibition zones against Gram-negative strains (E. coli and P. aeruginosa) as well as Gram-positive strains (S. aureus and B. subtilis). To further validate and refine the docking outcomes, molecular dynamics (MD) simulations were performed, providing detailed insights into the dynamic stability, conformational adaptability, hydrogen-bond persistence, and overall binding energetics of the most promising ligand–protein complexes. Density functional theory (DFT) calculations provided valuable insights into the electronic properties, stability, and reactivity of the compounds. The study successfully identified targeted compounds exhibiting significant antiviral/anti–SARS-CoV-2 potential using the pharmacophore POM model, highlighting their predicted ability to inhibit crucial viral proteins. The structures of the synthesized compounds were confirmed using a range of spectroscopic techniques, including FT IR, 1H NMR, 13C NMR, and mass spectrometry, ensuring the successful synthesis of the bioactive derivatives.