title: Synthesis and Antibacterial Activity of Novel Pleuromutilin Derivatives.
abstract: 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 antibacterial 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.
authors.affiliation: Key Laboratory of Veterinary Drug Safety Evaluation and Residues Research, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences.
authors.forename: Huixian
authors.initials: H
authors.lastname: Liu
authors.forename: Sui
authors.initials: S
authors.lastname: Xiao
authors.forename: Depeng
authors.initials: D
authors.lastname: Zhang
authors.forename: Shuhua
authors.initials: S
authors.lastname: Mu
authors.forename: Lifang
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
authors.forename: Feiqun
authors.initials: F
authors.lastname: Xue
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology; D013293:Enterococcus faecalis / Q000187:drug effects / Q000254:growth & development; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D010458:Peptidyl Transferases / Q000378:metabolism; D011083:Polycyclic Compounds; D012269:Ribosomal Proteins / Q000378:metabolism; D054681:Ribosome Subunits, Large, Bacterial / Q000378:metabolism; D013210:Staphylococcus / Q000187:drug effects / Q000254:growth & development; D013291:Streptococcus / Q000187:drug effects / Q000254:growth & development; D000097567:Pleuromutilins
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; D010458:Peptidyl Transferases; D011083:Polycyclic Compounds; D012269:Ribosomal Proteins; D000097567:Pleuromutilins