This title appears in the Scientific Report :
2020
Please use the identifier:
http://hdl.handle.net/2128/26511 in citations.
Please use the identifier: http://dx.doi.org/10.1021/acsmedchemlett.0c00381 in citations.
Semisynthetic Analogs of the Antibiotic Fidaxomicin—Design, Synthesis, and Biological Evaluation
Semisynthetic Analogs of the Antibiotic Fidaxomicin—Design, Synthesis, and Biological Evaluation
The glycoslated macrocyclic antibiotic fidaxomicin (1, tiacumicin B, lipiarmycin A3) displays good to excellent activity against Gram-positive bacteria and was approved for the treatment of Clostridium difficile infections (CDI). Among the main limitations for this compound, its low water solubility...
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Personal Name(s): | Dorst, Andrea |
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Berg, Regina / Gertzen, Christoph G. W. / Schäfle, Daniel / Zerbe, Katja / Gwerder, Myriam / Schnell, Simon D. / Sander, Peter / Gohlke, Holger / Gademann, Karl (Corresponding author) | |
Contributing Institute: |
Strukturbiochemie; IBI-7 John von Neumann - Institut für Computing; NIC Jülich Supercomputing Center; JSC |
Published in: | ACS medicinal chemistry letters, 11 (2020) 12, S. 2414–2420 |
Imprint: |
Washington, DC
ACS
2020
|
DOI: |
10.1021/acsmedchemlett.0c00381 |
Document Type: |
Journal Article |
Research Program: |
Forschergruppe Gohlke Computational Science and Mathematical Methods |
Link: |
OpenAccess OpenAccess OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.1021/acsmedchemlett.0c00381 in citations.
The glycoslated macrocyclic antibiotic fidaxomicin (1, tiacumicin B, lipiarmycin A3) displays good to excellent activity against Gram-positive bacteria and was approved for the treatment of Clostridium difficile infections (CDI). Among the main limitations for this compound, its low water solubility impacts further clinical uses. We report on the synthesis of new fidaxomicin derivatives based on structural design and utilizing an operationally simple one-step protecting group-free preparative approach from the natural product. An increase in solubility of up to 25-fold with largely retained activity was observed. Furthermore, hybrid antibiotics were prepared that show improved antibiotic activities. |