Design and synthesis of thiazole derivatives as potent FabH inhibitors with antibacterial activity

•Thiazole derivatives have been synthesized and evaluated as potent FabH inhibitors.•Compound 5f has shown the best antibacterial activity.•Docking simulation and the QSAR study with DS 3.5 was conducted.

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.

Graphical abstractCompounds of novel thiazole derivatives containing amide skeleton were synthesized, isolated and evaluated for their antibacterial and FabH inhibitory activity. Docking simulation and the QSAR study was conducted.Figure optionsDownload full-size imageDownload as PowerPoint slide