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Synthetic mimics of antimicrobial peptides from triaryl scaffolds.

ABSTRACT: In this report, we describe the synthesis of a new series of small amphiphilic aromatic compounds that mimic the essential properties of cationic antimicrobial peptides using Suzuki-Miyaura coupling. The new design allowed the easy tuning of the conformational restriction, controlled by introduction of intramolecular hydrogen bonds, and the overall hydrophobicity by modifications to the central ring and the side chains. This approach allowed us to better understand the influence of these features on the antimicrobial activity and selectivity. We found that the overall hydrophobicity had a more significant impact on antimicrobial and hemolytic activity than the conformational stiffness. A novel compound was discovered which has MICs of 0.78 ?g/mL against S. Aureus and 6.25 ?g/mL against E. Coli, similar to the well-known antimicrobial peptide, MSI-78.

SUBMITTER: Thaker HD

PROVIDER: S-EPMC3072574 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Synthetic mimics of antimicrobial peptides from triaryl scaffolds.

Thaker Hitesh D HD Sgolastra Federica F Clements Dylan D Scott Richard W RW Tew Gregory N GN

Journal of medicinal chemistry 20110309 7

In this report, we describe the synthesis of a new series of small amphiphilic aromatic compounds that mimic the essential properties of cationic antimicrobial peptides using Suzuki-Miyaura coupling. The new design allowed the easy tuning of the conformational restriction, controlled by introduction of intramolecular hydrogen bonds, and the overall hydrophobicity by modifications to the central ring and the side chains. This approach allowed us to better understand the influence of these feature ...[more]

PMID: 21388190

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