title: Design, synthesis and antibacterial activity studies of thiazole derivatives as potent ecKAS III inhibitors.
abstract: Two series of thiazole derivatives containing amide skeleton were synthesized and developed as potent Escherichia coli β-ketoacyl-(acyl-carrier-protein) synthase III (ecKAS III) inhibitors. All the 24 new synthesized compounds were assayed for antibacterial activity against the respective Gram-negative and Gram-positive bacterial strains, including E. coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. In which, 10 compounds with broad-spectrum antibacterial activities were further tested for their ecKAS III inhibitory activity. Last, we have successfully found that compound 4e showed both the promising broad antibacterial activity with MIC of 1.56-6.25μg/mL against the representative bacterial stains, and also processed the most potent ecKAS III inhibitory activity with IC50 of 5.3μM. In addition, docking simulation also carried out in this study to give a potent prediction binding mode between the small molecule and ecKAS III (PDB code: 1hnj) protein.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Kui
authors.initials: K
authors.lastname: Cheng
authors.forename: Jia-Yu
authors.initials: JY
authors.lastname: Xue
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D001665:Binding Sites; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D013844:Thiazoles; C077402:3-ketoacyl-acyl carrier protein synthase III; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase