Design, synthesis and biological evaluation of metronidazole-thiazole derivatives as antibacterial inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 24; no. 22; p. 5279
• Main Authors: Qin, Ya-Juan, Wang, Peng-Fei, Makawana, Jigar A, Wang, Zhong-Chang, Wang, Ze-Nan, Yan-Gu, Jiang, Ai-Qin, Zhu, Hai-Liang
• Format: Journal Article
• Language: English
• Published: England 15.11.2014
• Subjects: Acetyltransferases - antagonists & inhibitors; Acetyltransferases - metabolism; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - metabolism; Anti-Bacterial Agents - pharmacology; Binding Sites; Cell Line; Cell Survival - drug effects; Drug Design; Escherichia coli - metabolism; Escherichia coli Proteins - antagonists & inhibitors; Escherichia coli Proteins - metabolism; Fatty Acid Synthase, Type II - antagonists & inhibitors; Fatty Acid Synthase, Type II - metabolism; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Humans; Metronidazole - chemistry; Microbial Sensitivity Tests; Molecular Docking Simulation; Protein Structure, Tertiary; Thiazoles - chemistry
• ISSN: 1464-3405

A series of metronidazole–thiazole derivatives has been designed, synthesized and evaluated as potential antibacterial inhibitors. All the synthesized compounds were determined by elemental analysis, (1)H NMR and MS. They were also tested for antibacterial activity against Escherichia coli, Bacillus thuringiensis, Bacillus subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The results showed that compound 5 e exhibited the most potent inhibitory activity against E. coli FabH with IC50 of 4.9 lM. Molecular modeling simulation studies were performed in order to predict the biological activity of proposed compounds. Toxicity assay of compounds 5 a, 5 b, 5 d, 5 e, 5 g and 5 i showed that they were noncytotoxic against human macrophage. The results revealed that these compounds offered remarkable viability.