Abstract
Beta-ketoacyl-acyl carrier protein synthase III (KAS III) initiates bacterial fatty acid biosynthesis, making it one of the most promising condensing enzymes. In a previous study, we developed three pharmacophore maps from receptor-oriented pharmacophore-based in silico screening and proposed a potent antimicrobial inhibitor for KAS III. Using these pharmacophore maps, we examined a natural product database and chose 4 natural compounds as possible KAS III inhibitors. Here, we propose that YKAF01 (3,6-dihydroxyflavone) and YKAF04, 3-(4-hydroxyphenyl)-1-(2,4,6-tri-hydroxyphenyl)propan-1-one (or 4,2',4',6'-tetra-hydroxychalcone, phloretin) are potent antimicrobial inhibitors of KAS III with high binding affinity. In particular, these compounds display an excellent antimicrobial effect against Staphylococcus aureus and MRSA in the range of 16-32 microM.
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 / antagonists & inhibitors*
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3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / metabolism*
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Anti-Infective Agents / chemistry*
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Anti-Infective Agents / pharmacology*
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Anti-Infective Agents / toxicity
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Cell Line
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Cell Survival / drug effects
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Flavonoids / chemistry
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Flavonoids / pharmacology
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Flavonoids / toxicity
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Gram-Positive Bacteria / drug effects*
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Gram-Positive Bacteria / growth & development
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Humans
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Magnetic Resonance Spectroscopy
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Methicillin-Resistant Staphylococcus aureus / drug effects
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Methicillin-Resistant Staphylococcus aureus / growth & development
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Models, Molecular
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Molecular Structure
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Phloretin / chemistry
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Phloretin / pharmacology
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Phloretin / toxicity
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Protein Binding
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Spectrometry, Fluorescence
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Staphylococcus aureus / drug effects
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Staphylococcus aureus / growth & development
Substances
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Anti-Infective Agents
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Flavonoids
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3-ketoacyl-acyl carrier protein synthase III
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3-Oxoacyl-(Acyl-Carrier-Protein) Synthase
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Phloretin