1443544-29-3Relevant academic research and scientific papers
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.
