Design and synthesis of novel deoxybenzoin derivatives as FabH inhibitors and anti-inflammatory agents.
Beta-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes the initial step of fatty acid biosynthesis via a type II fatty acid synthase in most bacteria. The important role of this essential enzyme combined with its unique structural features and ubiquitous occurrence in bacteria has made it an attractive new target for the development of new FabH inhibitors. The synthesis and biological evaluation halide-deoxybenzoins derivatives are described in this Letter. Potent FabH inhibitory and selective anti-Gram-negative bacteria activities were observed in deoxybenzoin derivatives. Furthermore, compound 19 was able to reduce the ECE-induced IL-8 production in gastric mucosal cells significantly. Based on the biological data and molecular docking, compound 19 is a potential FabH inhibitor and anti-inflammatory agent deserving further research.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People's Republic of China.
Huan-Qiu
HQ
Li
Yin
Y
Luo
Peng-Cheng
PC
Lv
Lei
L
Shi
Chang-Hong
CH
Liu
Hai-Liang
HL
Zhu
D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D001573:Benzoin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D008958:Models, Molecular
D000893:Anti-Inflammatory Agents; D001426:Bacterial Proteins; C492807:deoxybenzoin; D001573:Benzoin