Design and synthesis of thiazole derivatives as potent FabH inhibitors with antibacterial activity
| Autor: | Jian Sun, Jing-Ran Li, Fei Fang, Jing-Jun Dong, Wei-Ming Zhang, Dong-Dong Li, Hai-Liang Zhu, Rong-Rong Wang, Qian-Ru Du |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Quantitative structure–activity relationship
Stereochemistry chemistry.chemical_compound Structure-Activity Relationship Acetyltransferases Drug Discovery 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase Escherichia coli Fatty Acid Synthase Type II Humans MTT assay Thiazole IC50 Escherichia coli Infections Pharmacology chemistry.chemical_classification Aromatic acid Bacteria Escherichia coli Proteins Organic Chemistry Fatty acid General Medicine Bacterial Infections Combinatorial chemistry Anti-Bacterial Agents Molecular Docking Simulation Thiazoles chemistry Docking (molecular) Drug Design Antibacterial activity |
| Zdroj: | European journal of medicinal chemistry. 75 |
| ISSN: | 1768-3254 |
| Popis: | Components of fatty acid biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents. Compounds of series A (4a–4g) and series B (5a–5g) 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, 4k, 4l, 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. |
| Databáze: | OpenAIRE |
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