Abstract
A series of 4-hydroxycoumarin derivatives were designed and synthesized in order to find some more potent antibacterial drugs. Their antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus were tested. These compounds showed good antibacterial activities against Gram-positive strains. Compound 4 g represented the most potent antibacterial activity against Bacillus subtilis and S. aureus with MIC of 0.236, 0.355 μg/mL, respectively. What's more, it showed the most potent activity against SaFabI with IC50 of 0.57 μM. Molecular docking of 4 g into S. aureus Enoyl-ACP-reductase active site were performed to determine the probable binding mode, while the QSAR model was built to check the previous work as well as to introduce new directions.
Keywords:
3D-QSAR; Antibacterial activities; Coumarin derivatives; Molecular docking; SaFabI.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / pharmacology*
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Anti-Bacterial Agents / toxicity
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Bacillus subtilis / drug effects
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Bacteria / drug effects*
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Binding Sites
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Catalytic Domain
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Coumarins / chemistry*
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Coumarins / metabolism
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Coumarins / pharmacology*
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Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / chemistry
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Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / metabolism
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Erythrocytes / cytology
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Erythrocytes / drug effects
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Escherichia coli / drug effects
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Hemolysis / drug effects
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Humans
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Microbial Sensitivity Tests
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Molecular Docking Simulation
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Piperazine
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Piperazines / chemistry*
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Protein Binding
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Pseudomonas aeruginosa / drug effects
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Quantitative Structure-Activity Relationship
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Staphylococcus aureus / drug effects
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Staphylococcus aureus / enzymology
Substances
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Anti-Bacterial Agents
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Coumarins
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Piperazines
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Piperazine
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Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)