Abstract
Semi-synthetic water-soluble analogs were synthesized from nocathiacin I through the formation of a versatile intermediate nocathiacin amine 5, and subsequent transformation via reductive amination, acylation or urea formation. Several of the novel analogs displayed much improved aqueous solubility over 1, while retained antibacterial activity. Compound 15 and 16 from the amide series, demonstrated excellent in vitro and in vivo antibacterial activity.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology
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Enterococcus faecalis / drug effects
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Intercellular Signaling Peptides and Proteins
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Microbial Sensitivity Tests
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Peptides / chemical synthesis
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Peptides / chemistry*
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Peptides / pharmacology
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Peptides, Cyclic / chemical synthesis*
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Peptides, Cyclic / chemistry
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Peptides, Cyclic / pharmacology
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Solubility
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Staphylococcus aureus / drug effects
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Streptococcus pneumoniae / drug effects
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Structure-Activity Relationship
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Thiazoles / chemical synthesis*
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Thiazoles / chemistry
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Thiazoles / pharmacology
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Water / chemistry
Substances
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Anti-Bacterial Agents
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Intercellular Signaling Peptides and Proteins
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Peptides
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Peptides, Cyclic
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Thiazoles
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nocathiacin I
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Water