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Design, synthesis, and structure–activity relationship studies of novel pleuromutilin derivatives having a piperazine ring
Author(s) -
Luo Jian,
Yang QiuE,
Yang YuanYuan,
Tang YouZhi,
Liu YaHong
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12799
Subject(s) - piperazine , antibacterial activity , chemistry , escherichia coli , staphylococcus aureus , in vitro , agar dilution , combinatorial chemistry , ring (chemistry) , ribosome , minimum inhibitory concentration , stereochemistry , biochemistry , organic chemistry , biology , bacteria , genetics , gene , rna
A series of novel pleuromutilin derivatives possessing piperazine moieties were synthesized under mild conditions. The in vitro antibacterial activities of these derivatives against Staphylococcus aureus and Escherichia coli were tested by the agar dilution method. Structure–activity relationship studies resulted in compounds 11b , 13b , and 14a with the most potent in vitro antibacterial activity among the series (minimal inhibitory concentration = 0.0625–0.125 μ g/mL). The binding of compounds 11b , 13b , and 14a to the E. coli ribosome was investigated by molecular modeling, and it was found that there is a reasonable correlation between the binding free energy and the antibacterial activity.