Abstract
FabH, β-ketoacyl-acyl carrier protein (ACP) synthase III, is critically important to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and Gram-negative bacteria. A series of novel secnidazole derivatives (1-20) were synthesized and fully characterized by spectroscopic methods and elemental analysis. Among these compounds, 6, 8, 11, 13, 14, 16-20 were reported for the first time. These compounds were tested for antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. The compounds inhibitory assay and docking simulation indicated that compound 20 (E)-2-(2-methyl-5-nitro-1H-imidazol-1-yl)-N'-(3,4,5-trimethylbenzylidene)acetohydrazide with MIC of 3.13-6.25 μg/mL against the tested bacterial strains was a potent inhibitor of Escherichia coli FabH.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3-Oxoacyl-(Acyl-Carrier-Protein) Synthase
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Acetyltransferases / antagonists & inhibitors
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Acetyltransferases / chemistry*
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Acetyltransferases / metabolism
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / pharmacology
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Bacillus subtilis / drug effects
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Bacillus subtilis / enzymology
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Bacillus subtilis / growth & development
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Escherichia coli / drug effects
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Escherichia coli / enzymology
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Escherichia coli / growth & development
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Escherichia coli Proteins / antagonists & inhibitors
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Escherichia coli Proteins / chemistry*
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Escherichia coli Proteins / metabolism
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Fatty Acid Synthase, Type II / antagonists & inhibitors
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Fatty Acid Synthase, Type II / chemistry
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Fatty Acid Synthase, Type II / metabolism
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Metronidazole / analogs & derivatives*
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Metronidazole / chemical synthesis
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Metronidazole / pharmacology
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Microbial Sensitivity Tests
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Molecular Docking Simulation
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Pseudomonas aeruginosa / drug effects
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Pseudomonas aeruginosa / enzymology
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Pseudomonas aeruginosa / growth & development
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Schiff Bases / chemical synthesis*
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Schiff Bases / pharmacology
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Staphylococcus aureus / drug effects
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Staphylococcus aureus / enzymology
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Staphylococcus aureus / growth & development
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Enzyme Inhibitors
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Escherichia coli Proteins
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Schiff Bases
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Metronidazole
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Acetyltransferases
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fabH protein, E coli
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3-Oxoacyl-(Acyl-Carrier-Protein) Synthase
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Fatty Acid Synthase, Type II
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secnidazole