Unveiling the antibacterial efficacy of thiazolo [3,2‐a] pyrimidine: Synthesis, molecular docking, and molecular dynamic simulation.

Two series of C‐Mannich base derivatives were synthesized and evaluated through the reaction of formaldehyde, two thiazolo‐pyrimidine compounds, and various 2°‐amines. The chemical structures and inherent properties of the synthesized compounds were authenticated using a variety of spectroscopic techniques. The aseptic bactericidal potential of the compounds was assessed alongside five common bacterial microbes, with Ampicillin employed as the reference drug. Compounds 9b and 9d demonstrated comparable antibacterial activity to ampicillin against Bacillus subtilis and Bacillus megaterium, respectively, at 100 μg/mL. Furthermore, compounds 9f and 10f exhibited noteworthy action against Staphylococcus aureus (MIC: 250 μg/mL). Compounds 10b and 10f displayed excellent efficacy versus Escherichia coli, boasting (MIC: 50 μg/mL). Molecular docking studies elucidated the necessary connections and energies of molecular entities with the E. coli DNA gyrase B enzyme, a pivotal target in bacterial DNA replication. Further thermodynamic stability of the ligand‐receptor complex of 10b and 10f were further validated though 200 ns molecular dynamics simulation. The findings highlight the potential of these synthesized derivatives as effective antibacterial agents and provide valuable insights into their mechanism of action. Highlights: Two series of C‐Mannich base derivatives were synthesized by reacting formaldehyde, two thiazolo[3,2‐a] pyrimidine compounds, and seven heterocyclic amines.The antibacterial potential of the compounds was evaluated against five common bacterial pathogens, with Ampicillin as the reference drug.Compounds 9b and 9d showed comparable antibacterial activity to Ampicillin against Bacillus subtilis and Bacillus megaterium, respectively, at 100 μg/mL.Compounds 9 f and 10 f exhibited notable activity against Staphylococcus aureus, with MIC values of 250 μg/mL.Compounds 10b and 10 f displayed excellent efficacy against Escherichia coli, with MIC values of 50 μg/mL.Molecular docking studies revealed the binding interactions and energies of the compounds with the E. coli DNA gyrase B enzyme, a crucial target in bacterial DNA replication.The binding stability of promising compounds 10b and 10 f was further validated through 200 ns molecular dynamics (MD) simulations. [ABSTRACT FROM AUTHOR]