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Synthetic and Biological Studies on New Urea and Triazole Containing Cystobactamid Derivatives
Author(s) -
Planke Therese,
Cirnski Katarina,
Herrmann Jennifer,
Müller Rolf,
Kirschning Andreas
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201904073
Subject(s) - amide , chemistry , ring (chemistry) , urea , peptide bond , hydrolysis , triazole , stereochemistry , combinatorial chemistry , enzyme , organic chemistry
Cystobactamids belong to the group of arene‐based oligoamides that effectively inhibit bacterial type IIa topoisomerases. Cystobactamid 861‐2 is the most active member of these antibiotics. Most amide bonds present in the cystobactamids link benzoic acids with anilines and it was found that some of these amide bonds undergo chemical and enzymatic hydrolysis, especially the one linking ring C with ring D. This work reports on the chemical synthesis and biological evaluation of thirteen new cystobactamids that still contain the methoxyaspartate hinge. However, we exchanged selected amide bonds either by the urea or the triazole groups and modified ring A in the latter case. While hydrolytic stability could be improved with these structural substitutes, the high antibacterial potency of cystobactamid 861‐2 could only be preserved in selected cases. This includes derivatives, in which the urea group is positioned between rings A and B and where the triazole is found between rings C and D.