Design, synthesis, molecular docking, molecular dynamic simulation, and MMGBSA analysis of 7-O-substituted 5-hydroxy flavone derivatives.

A series of chrysin derivatives were designed, synthesized, and evaluated for their antibacterial activity against four different bacterial strains. We have synthesized new propyl-substituted and butyl-substituted chrysin-piperazine derivatives, which show marvellous inhibition against and . The free hydroxyl group at the C-5 position of chrysin improved therapeutic efficacy and was a beneficial formulation for chemotherapy. All synthesized compounds were confirmed by various spectroscopic techniques such as IR, NMR, HPLC, and mass spectrometry. The compounds exhibited moderate to good inhibition, and their structure-activity relationship (SAR) has also been illustrated. Among the synthesised compounds, compounds and were the most active against and , with 12.5 g/mL MICs; additionally, compound exhibits significant activity on both the and stains. Based on the promising activity profile and docking score of compound , it was selected for 100 ns MD simulation and post-dynamic binding free energy analysis within the active sites of TyrRS (PDB ID: 1JIJ) and DNA GyrB (PDB ID: 6YD9) to investigate the stability of molecular contacts and to establish how the newly synthesized inhibitors fit together in the most stable conformations.Communicated by Ramaswamy H. Sarma.