Study of Schiff-Base-Derived with Dioxygenated Rings and Nitrogen Heterocycle as Potential β-Ketoacyl-acyl Carrier Protein Synthase III (FabH) Inhibitors.
Fatty acid synthesis (FAS) is an essential metabolism during the whole growth and development process of the bacterial. Several key enzymes which involved in this biosynthetic pathway have been considered as useful targets for the development of new antibacterial agents. Among them, β-ketoacyl-acyl carrier protein synthase III (FabH) is the most magnetic target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved of both Gram-positive and Gram-negative bacteria. Following the previous researches, Schiff-based derivatives with dioxygenated rings and N-heterocycle were synthesized in succession, and their biological activities as potential FabH inhibitors were evaluated in this paper. Among these 15 compounds, compound 2E exhibited the best antibacterial activities with minimum inhibitory concentration (MIC) values 1.56-3.13 mg/mL against the tested bacterial strains and showed the most powerful Escherichia coli (E. coli) FabH inhibitory activities with IC50of 2.1 µM. Also the conceivable binding conformation of placing compound 2E into the E. coli FabH active site was affirmed docking simulation.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University.
Yang
Y
Zhou
Yu-Shun
YS
Yang
Xiao-Da
XD
Song
Liang
L
Lu
Hai-Liang
HL
Zhu
D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000037:antagonists & inhibitors*; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D017672:Nitrogen Compounds / Q000737:chemistry* / Q000494:pharmacology; D012545:Schiff Bases / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D017672:Nitrogen Compounds; D012545:Schiff Bases; C077402:3-ketoacyl-acyl carrier protein synthase III; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase