Design, synthesis and molecular docking of 1,4-benzodioxane thiazolidinedione piperazine derivatives as FabH inhibitors.
A series of novel 1,4-benzodioxane thiazolidinedione piperazine derivatives targeting FabH were designed and synthesized. The compounds exhibited better inhibitory activity against Gram-negative bacteria by computer-assisted screening, antibacterial activity test and E. coli FabH inhibitory activity test, wherein compound 6j exhibited the most significant inhibitory activity (MIC = 1.80 μΜ for P. aeruginosa, MIC = 1.56 μΜ for E. coli). Besides, compound 6j still showed the best E. coli FabH inhibitory activity (IC50 = 0.06 μΜ). Moreover, the antibacterial activities of all compounds were strongly correlated with the inhibitory ability of FabH, with a correlation coefficient of 0.954. Computational docking studies also showed that compound 6j has interacting with FabH key residues in the active site.
['Sun|Juan|J|', 'He|Wen|W|', 'Liu|Han-Yu|HY|', 'Qin|Jie|J|', 'Ye|Chun-Lin|CL|']
D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase D000123:Acetyltransferases D004147:Dioxins D004305:Dose-Response Relationship, Drug D015195:Drug Design D004791:Enzyme Inhibitors D004926:Escherichia coli D029968:Escherichia coli Proteins D054889:Fatty Acid Synthase, Type II D062105:Molecular Docking Simulation D015394:Molecular Structure D000077489:Piperazine D013329:Structure-Activity Relationship D045162:Thiazolidinediones
Molecular docking Thiazolidinedione Antibacterial activity FabH inhibitory 1,4-benzodioxane derivatives