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

AbstractA 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 E. coli and S. aureus. The free hydroxyl group at the C-5 position of chrysin improved therapeutic efficacy in vivo 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 4 and 10 were the most active against S. pyogenes and E. coli, with 12.5 g/mL MICs; additionally, compound 12 exhibits significant activity on both the S. aureus and E. coli stains. Based on the promising activity profile and docking score of compound 12, it was selected for 100 ns MD simulation and post-dynamic binding free energy analysis within the active sites of S. aureus TyrRS (PDB ID: 1JIJ) and E. coli 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. SarmaKeywords: Flavone derivativesmolecular dockingMD simulationsynthesisand MMGBSA analysis AcknowledgmentThis research was supported by Sardar Vallabhbhai National Institute of Technology. Authors would like to thank Mahrshee laboratory, Darshan health care and Jaydev chemical for gifting piperazine derivatives. Authors are also thankful to Micro care laboratory and Nirma university for the analysis of synthesized compounds.Disclosure statementNo potential conflict of interest was reported by the author(s).Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.