1443544-38-4Relevant academic research and scientific papers
Design, synthesis and biological activity of novel demethylvancomycin dimers against vancomycin-resistant enterococcus faecalis
Jiang, Yong-Wei,Xu, Liang,Fu, Wei,Lin, Hua,Yu, Jian-Ming,Sun, Xun
, p. 3527 - 3533 (2018)
The emergence of resistance to vancomycin and other glycopeptide antibiotics is a serious concern in clinical practice and has prompted intensive efforts to develop analogues that may overcome the resistance. One of major strategies to enhancing anti-vancomycin-resistant enterococci (VRE) activity emerged in recent years was connecting two vancomycin molecules by covalent linkers. Herein, we reported the design and synthesis of three different covalently linked demethylvancomycin dimers 7a-c by applying click chemistry. Interestingly, these dimers restored their activities against VRE. Furthermore, the interactions of molecules with peptidoglycan were also investigated via computer modelling.
Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug-Resistant Bacteria
Chang, Jun,Zhang, Si-Ji,Jiang, Yong-Wei,Xu, Liang,Yu, Jian-Ming,Zhou, Wen-Jiang,Sun, Xun
, p. 976 - 984 (2013/07/27)
Five novel N-substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure-based approach. The invitro antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA), gentamicin-resistant Enterococcus faecalis (GRE), methicillin-resistant Streptococcus pneumoniae (MRS), and vancomycin-resistant Enterococcus faecalis (VRE) were evaluated. One of the compounds, N-(6-phenylheptyl)demethylvancomycin (12a), was found to exhibit more potent antibacterial activity than vancomycin and demethylvancomycin. Compound 12a was also found to be ～18-fold more efficacious than vancomycin against MRSA; however, the two compounds were found to have similar efficacy against MRS. Furthermore, compound 12a exhibited a favorable pharmacokinetic profile with a half-life of 5.11±0.52h, which is longer than that of vancomycin (4.3±1.9h). These results suggest that 12a is a promising antibacterial drug candidate for further preclinical evaluation.
