title: Design, synthesis and biological activity evaluation of novel 2,6-difluorobenzamide derivatives through FtsZ inhibition.
abstract: Novel series of 3-substituted 2,6-difluorobenzamide derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their in vitro antibacterial activity against various phenotype of Gram-positive and Gram-negative bacteria, and their cell division inhibitory activity against three representative strains. As a result, 3-chloroalkoxy derivative 7, 3-bromoalkoxy derivative 12 and 3-alkyloxy derivative 17 were found to exhibit the best antibacterial activity against Bacillus subtilis with MICs of 0.25-1μg/mL, and good activity (MIC<10μg/mL) against both susceptible and resistant Staphylococcus aureus. Additionally, all the three compounds displayed potent cell division inhibitory activity with MIC values of below 1μg/mL against Bacillus subtilis and Staphylococcus aureus.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, PR China.
authors.forename: Fangchao
authors.initials: F
authors.lastname: Bi
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, PR China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, PR China.
authors.forename: Yinhu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide 5001, Australia.
authors.forename: Henrietta
authors.initials: H
authors.lastname: Venter
authors.affiliation: School of Pharmacy & Medical Sciences, Sansom Institute for Health Research, University of South Australia, GPO Box 2471, Adelaide 5001, Australia.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Semple
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, PR China. Electronic address: mashutao@sdu.edu.cn.
authors.forename: Shutao
authors.initials: S
authors.lastname: Ma
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D001549:Benzamides / Q000737:chemistry* / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001549:Benzamides; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; C078231:2,6-difluorobenzamide
keywords: Benzamide derivatives; Biological activity; Design and synthesis; FtsZ inhibition