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  • Title: Antimicrobial natural products as beta-ketoacyl-acyl carrier protein synthase III inhibitors.
    Author: Lee JY, Jeong KW, Shin S, Lee JU, Kim Y.
    Journal: Bioorg Med Chem; 2009 Aug 01; 17(15):5408-13. PubMed ID: 19595597.
    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.
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