Details
| Original language | English |
|---|---|
| Pages (from-to) | 4289-4296 |
| Number of pages | 8 |
| Journal | Chemistry - A European Journal |
| Volume | 26 |
| Issue number | 19 |
| Early online date | 13 Dec 2019 |
| Publication status | Published - 1 Apr 2020 |
Abstract
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.
Keywords
- amides, antibiotics, chemical synthesis, medicinal chemistry, triazoles, urea
ASJC Scopus subject areas
- Chemical Engineering(all)
- Catalysis
- Chemistry(all)
- Organic Chemistry
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In: Chemistry - A European Journal, Vol. 26, No. 19, 01.04.2020, p. 4289-4296.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Synthetic and Biological Studies on New Urea and Triazole Containing Cystobactamid Derivatives
AU - Planke, Therese
AU - Cirnski, Katarina
AU - Herrmann, Jennifer
AU - Müller, Rolf
AU - Kirschning, Andreas
N1 - Funding information: This work was supported by the German Center for Infection Research (DZIF) and the Bundesministerium für Bildung und Forschung (BMBF; project OpCyBac).
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - amides
KW - antibiotics
KW - chemical synthesis
KW - medicinal chemistry
KW - triazoles
KW - urea
UR - http://www.scopus.com/inward/record.url?scp=85081301578&partnerID=8YFLogxK
U2 - 10.1002/chem.201904073
DO - 10.1002/chem.201904073
M3 - Article
C2 - 31834653
AN - SCOPUS:85081301578
VL - 26
SP - 4289
EP - 4296
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
SN - 0947-6539
IS - 19
ER -