61429-04-7Relevant academic research and scientific papers
Semisynthetic Analogs of the Antibiotic Fidaxomicin - Design, Synthesis, and Biological Evaluation
Dorst, Andrea,Berg, Regina,Gertzen, Christoph G. W.,Sch?fle, Daniel,Zerbe, Katja,Gwerder, Myriam,Schnell, Simon D.,Sander, Peter,Gohlke, Holger,Gademann, Karl
supporting information, p. 2414 - 2420 (2020/11/18)
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.
TIACUMICIN DERIVATIVES AND THEIR USE AS ANTIBIOTICS
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Paragraph 0172; 0173, (2019/07/18)
The invention relates to a compound according to formula (1) wherein R1 to R4 and X are independently from each other a small functional group and R5 is -OH, or -O-Ln-Rap-Rbq-Lt-Rar-Rbs-Re, -O-Ln-Rbq-Rd-Lt-Rbs-Re with L being an alkyl linker, Ra being carbonyl, carboxyl or carboxamide, Rb being a cyclic moiety, Rd being a polyether linker and Re being a small functional end group, fluorescent dye or antibiotic with the proviso that the compound is not fidaxomicin. Furthermore, the invention relates to the use of the compound in the treatment of disease and the use in treating infections and/or bacterial infections caused by drug resistant bacteria.
Heterodimeric Rifampicin–Tobramycin conjugates break intrinsic resistance of Pseudomonas aeruginosa to doxycycline and chloramphenicol in vitro and in a Galleria mellonella in vivo model
Idowu, Temilolu,Arthur, Gilbert,Zhanel, George G.,Schweizer, Frank
, p. 16 - 32 (2019/04/25)
Intrinsic resistance in Pseudomonas aeruginosa, defined by chromosomally encoded low outer membrane permeability and constitutively over-expressed efflux pumps, is a major reason why the pathogen is refractory to many antibiotics. Herein, we report that h
Synthesis of Tridecaptin-Antibiotic Conjugates with in Vivo Activity against Gram-Negative Bacteria
Cochrane, Stephen A.,Li, Xuefeng,He, Sisi,Yu, Min,Wu, Min,Vederas, John C.
supporting information, p. 9779 - 9785 (2016/01/12)
A series of tridecaptin-antibiotic conjugates were synthesized and evaluated for in vitro and in vivo activity against Gram-negative bacteria. Covalently linking unacylated tridecaptin A1 (H-TriA1) to rifampicin, vancomycin, and erythromycin enhanced their activity in vitro but not by the same magnitude as coadministration of the peptide and these antibiotics. The antimicrobial activities of the conjugates were retained in vivo, with the H-TriA1-erythromycin conjugate proving a more effective treatment of Klebseilla pneumoniae infections in mice than erythromycin alone or in combination with H-TriA1.
