title: Novel lead compound optimization and synthesized based on the target structure of Xanthomonas oryzae pv. oryzae GlmU.
abstract: Bacterial leaf blight, caused by Xanthomonas oryzae pv. oryzae, is one of the most destructive diseases of rice worldwide. N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) was an attractive target for the development of antimicrobial agents. To develop novel, more potent and even more selective inhibitors of the uridyltransferase activity of Xanthomonas oryzae pv. oryzae GlmU (Xo-GlmU), three types of novel target compounds were optimized and synthesized based on the Xo-GlmU structure in this study. The biological testing results showed that all of the target compounds displayed the higher inhibition than the lead compound with the IC50 values in the 10.82-23.31 µM range, and the inhibition rates were increased by 30%-67%. The binding mode and the possible inhibitory mechanism of the target compounds in the active site were also analyzed by the molecular docking based on the uridyltransferase active site of Xo-GlmU.
authors.affiliation: College of Science, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Qi
authors.affiliation: College of Science, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Deng
authors.affiliation: College of Science, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.affiliation: College of Science, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Bangqiang
authors.initials: B
authors.lastname: Mao
authors.affiliation: College of Science, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Shengzhen
authors.initials: S
authors.lastname: Xu
authors.affiliation: College of Science, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Changshui
authors.initials: C
authors.lastname: Chen
authors.affiliation: College of Science, Huazhong Agricultural University, Wuhan 430070, China; Agricultural Bioinformatics Key Laboratory of Hubei Province, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: zqylty@163.com.
authors.forename: Qingye
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D060326:Chemistry Techniques, Synthetic; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D012275:Oryza / Q000382:microbiology; D013329:Structure-Activity Relationship; D014974:Xanthomonas / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D009713:Nucleotidyltransferases; C023226:UDPacetylglucosamine pyrophosphorylase
keywords: Bioactive assay; GlmU; Inhibitors; Lead compound optimization; Synthesis