Design,Synthesis And In Vitro Antibacterial Evaluation Of New FabI Inhibitors

Bacterial enoyl-ACP reductase(ENR)can catalyze the final step of the cyclic e xtension reaction in the fatty acid synthesis pathway of FAS type II,which means t he reduction of the C-C double bond of the enoyl intermediate.At the same time,it is the rate-limiting enzyme in the entire synthetic pathway,and it has also been i dentified as a target of antibacterial drugs.Since the biosynthesis of fatty acids in p athogenic microorganisms is critical to the viability of bacteria,the FASII pathway has attracted widespread attention from drug discovery workers in recent years.In this study,AFN-1252 with significant antibacterial activity was used as temp late,and its molecular design and structure modification based on receptor-ligand int eraction were carried out by DS-CDOCKER module in Discovery Studio 4.0 softwa re.Twenty-eight heterocyclic acrylamide compounds were designed,synthesized and screened for Gram-positive bacteria and Gram-positive bacteria simultaneously.The main results are as follows:1.Use Discovery Studio 4.0 software to perform simple processing on protein crystals with a PDB code of 4FS3 and use the AFN-1252 small molecule ligand as a positive control.The designed compounds are molecularly docked,and the resulti ng docking results are analyzed and their RMSD values are calculated.Finally,28 t arget compounds with potential antibacterial activity were obtained.2.28 substituted acrylamides,including 30 intermediates,were synthesized thro ugh the reactions of aldol condensation,reduction,Heck reaction,and hydrolysis.Al l the target heterocyclic acrylamide compounds were identified by spectral method i ncluding 1H-NMR,13C-NMR and high resolution mass spectroscopy.Additionally,al l the synthesized 28 compounds have not been reported.3.The double-dilution method of the test tube was used to determine the antib acterial activity of 28 compounds containing the heterocyclic group in the A series against common pathogenic bacteria such as Staphylococcus aureus,Escherichia coli,Salmonella,Bacillus subtilis,and Candida albicans.The results showed that most of the desired compounds were not active against Staphylococcus aureus,Salmonella,Bacillus subtilis,and Candida albicans.Among them,compound A13 had the high est inhibitory activity against Bacillus subtilis,and its MIC and MBC values were 4?g/m L and 16 ?g/m L,respectively.Compound 18 show medium antibacterial acti vity against Staphylococcus aureus,Candida albicans,and Bacillus subtilis.