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Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug‐Resistant Bacteria
Author(s) -
Chang Jun,
Zhang SiJi,
Jiang YongWei,
Xu Liang,
Yu JianMing,
Zhou WenJiang,
Sun Xun
Publication year - 2013
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201300011
Subject(s) - enterococcus faecalis , vancomycin , streptococcus pneumoniae , staphylococcus aureus , antibacterial activity , microbiology and biotechnology , methicillin resistant staphylococcus aureus , gentamicin , enterococcus , antibiotics , chemistry , antibacterial agent , bacteria , biology , genetics
Five novel N‐substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure‐based approach. The in vitro 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 ( 12 a ), was found to exhibit more potent antibacterial activity than vancomycin and demethylvancomycin. Compound 12 a 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 12 a exhibited a favorable pharmacokinetic profile with a half‐life of 5.11±0.52 h, which is longer than that of vancomycin (4.3±1.9 h). These results suggest that 12 a is a promising antibacterial drug candidate for further preclinical evaluation.