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Synthesis of short cationic antimicrobial peptidomimetics containing arginine analogues
Author(s) -
Baldassarre Leonardo,
Pinnen Francesco,
Cornacchia Catia,
Fornasari Erika,
Cellini Luigina,
Baffoni Marina,
Cacciatore Ivana
Publication year - 2012
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2435
Subject(s) - antimicrobial , peptidomimetic , staphylococcus epidermidis , chemistry , candida albicans , microbiology and biotechnology , staphylococcus aureus , biofilm , peptide , bacteria , biochemistry , biology , organic chemistry , genetics
Worldwide efforts are underway to develop new antimicrobial agents against bacterial resistance. To identify new compounds with a good antimicrobial profile, we designed and synthesized two series of small cationic antimicrobial peptidomimetics (1–8) containing unusual arginine mimetics (to introduce cationic charges) and several aromatic amino acids (bulky moieties to improve lipophilicity). Both series were screened for in vitro antibacterial activity against a representative panel of Gram‐positive ( Staphylococcus aureus and Staphylococcus epidermidis ) and Gram‐negative ( Escherichia coli and Klebsiella pneumoniae ) bacterial strains, and Candida albicans . The biological screening showed that peptidomimetics containing tryptophan residues are endowed with the best antimicrobial activity against S. aureus and S. epidermidis in respect to the other synthesized derivatives (MIC values range 7.5–50 µg/ml). Moreover, small antimicrobial peptidomimetics derivatives 2 and 5 showed an appreciable activity against the tested Gram‐negative bacteria and C. albicans . The most active compounds (1–2 and 5–6) have been tested against Gram‐positive established biofilm, too. Results showed that the biofilm inhibitory concentration values of these compounds were never up to 200 µg/ml. The replacement of tryptophan with phenylalanine or tyrosine resulted in considerable loss of the antibacterial action (compounds 3–4 and 7–8) against both Gram‐positive and Gram‐negative bacterial strains. Furthermore, by evaluating hemolytic activity, the synthesized compounds did not reveal cytotoxic activities, except for compound 5. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.