title: Design and synthesis of thiazole derivatives as potent FabH inhibitors with antibacterial activity.
abstract: Components of fatty acid biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents. Compounds of series A (4a-4 g) and series B (5a-5 g) were synthesized by the formation of an amine bond between aromatic acid and 4-phenylthiazol-2-amine or 4-(4-bromophenyl)thiazol-2-amine. These thiazole derivatives have evaluated as potent FabH inhibitors. Nineteen compounds (4b-4h, 4 k, 4 l, 5a-5h, 5k, 5l) are reported for the first time. Most of the synthesized compounds exhibited antibacterial activity in the MTT assay. The MIC value of these compounds ranged from 1.56 μg/mL to 100 μg/mL. Moreover, the tested compounds also showed FabH inhibition ability with IC50 value ranging from 5.8 μM to 48.1 μM. The IC50 values are near the MIC values. Compound 5f has exhibited the best antibacterial and Escherichia coli FabH inhibitory activity. Docking simulation and the QSAR study was conducted for learning about binding mode and the relationship between structure and activity.
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Jing-Ran
authors.initials: JR
authors.lastname: Li
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Li
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Wang
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Jing-Jun
authors.initials: JJ
authors.lastname: Dong
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Qian-Ru
authors.initials: QR
authors.lastname: Du
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Fang
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: botanyzh@163.com.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Zhang
authors.affiliation: Nanjing Institute for the Comprehensive Utilization of Wild Plant, Nanjing 210042, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D000123:Acetyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology; D001424:Bacterial Infections / Q000188:drug therapy / Q000201:enzymology / Q000382:microbiology; D015195:Drug Design; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000201:enzymology / Q000382:microbiology; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D054889:Fatty Acid Synthase, Type II / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; 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; D000123:Acetyltransferases; C557158:fabH protein, E coli; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D054889:Fatty Acid Synthase, Type II
keywords: 3D-QSAR; Antibacterial; FabH; Molecular docking; Thiazole derivatives