Synthesis and Antibacterial Activity of Novel Pleuromutilin Derivatives

Huixian Liu, Sui Xiao, Depeng Zhang, Shuhua Mu, Lifang Zhang, Xiaoyang Wang, Feiqun Xue
2015 Biological and Pharmaceutical Bulletin  
In this study we describe the design, synthesis, and antibacterial activity of novel pleuromutilin analogs. A series of new compounds containing piperazine and alkylamino or arylamino groups was synthesized. The new compounds were characterized via 1 H-NMR, 13 C-NMR, Fourier transform (FT)-IR and MS, and were further evaluated for their in vitro activity against seven Gram-positive, and one Gram-negative, pathogens. Antibacterial data revealed that all compounds exhibited moderate to good
more » ... cterial activities against sensitive Gram-positive pathogens. Specifically, 9d displayed the best activity: its activity to Staphylococcus aureus (ATCC25923) is 0.125 µg/mL, which is equal to the control compound tiamulin. The antibacterial activities of 9d to Streptococcus suis (minimum inhibitory concentration (MIC) of 2 µg/mL), Streptococcus agalactiae (MIC of 0.5 µg/mL), and Streptococcus dysgalactiae (MIC of 0.5 µg/mL) were also excellent compared with the control drug erythromycin (MIC of >128 µg/mL). The binding modes of these compounds with active sites were calculated using the programs of Molecular Operating Environment (MOE) and Pymol.
doi:10.1248/bpb.b15-00123 pmid:26133714 fatcat:p3xgono2rbb2he7g22npmm4zvm