Towards Squalamine Mimics: Synthesis and Antibacterial Activities of Head-to-Tail Dimeric Sterol[BOND]Polyamine Conjugates

Authors

  • Wen-Hua Chen,

    Corresponding author
    1. School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, P. R. China, (fax: +86-20-61648533)
    2. Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania 18015, USA
    • Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania 18015, USA
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  • Christine Wennersten,

    1. Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, 110 Francis St., LMOB-6A, Boston, MA 02215, USA
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  • Robert C. Moellering Jr.,

    1. Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, 110 Francis St., LMOB-6A, Boston, MA 02215, USA
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  • Steven L. Regen

    Corresponding author
    1. Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania 18015, USA
    • Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania 18015, USA
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Abstract

Four dimeric sterol[BOND]polyamine conjugates have been synthesized from the homo- and hetero-connection of monomeric sterol[BOND]polyamine analogs in a head-to-tail manner. These dimeric conjugates show strong antibacterial activity against a broad spectrum of Gram-positive bacteria, whereas their corresponding activities against Gram-negative bacteria are relatively moderate. Though no significant difference was observed in the activities of these conjugates, cholic acid-containing dimeric conjugates generally exhibit higher activities than the corresponding deoxycholic acid-derived analogs. This is in contrast to the finding that a monomeric deoxycholic acid-spermine conjugate was more active than the corresponding cholic acid-derived analog.

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