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Evaluation of Readily Accessible Azoles as Mimics of the Aromatic Ring of D ‐Phenylalanine in the Turn Region of Gramicidin S
Author(s) -
van der Knaap Matthijs,
Lageveen Lianne T.,
Busscher Henk J.,
MarsGroenendijk Roos,
Noort Daan,
Otero José M.,
LlamasSaiz Antonio L.,
van Raaij Mark J.,
van der Marel Gijsbert A.,
Overkleeft Herman S.,
Overhand Mark
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000539
Subject(s) - chemistry , moiety , gramicidin s , triazole , antibacterial activity , substituent , stereochemistry , gramicidin , phenylalanine , imidazole , residue (chemistry) , structure–activity relationship , organic chemistry , amino acid , bacteria , biochemistry , in vitro , biology , genetics , membrane
Abstract The influence of replacing the d‐ phenylalanine residue with substituted and unsubstituted azoles on the structure and biological activity of the antibiotic gramicidin S was investigated against a representative panel of Gram‐positive and Gram‐negative bacteria strains. Substituted triazole derivatives, obtained using a convergent synthetic strategy, are as active as gramicidin S, provided that any substituent on the triazole moiety is not too large. The unsubstituted triazole derivative was biologically less active than the parent natural product, gramicidin S. In general for the triazole series, the hemolytic activity could be correlated with the antibacterial activity, that is, the higher the antibacterial activity, the higher the toxicity towards blood cells. Interestingly, its imidazole counterpart showed high antibacterial activity, combined with significantly diminished hemolytic activity.