Chemical synthesis and biological activities of novel pleuromutilin derivatives with substituted amino moiety

Ruofeng Shang; Shengyu Wang; Ximing Xu; Yunpeng Yi; Wenzhu Guo; Yuliu; Jianping Liang

doi:10.1371/journal.pone.0082595

Chemical synthesis and biological activities of novel pleuromutilin derivatives with substituted amino moiety

PLoS One. 2013 Dec 23;8(12):e82595. doi: 10.1371/journal.pone.0082595. eCollection 2013.

Authors

Ruofeng Shang¹, Shengyu Wang², Ximing Xu³, Yunpeng Yi¹, Wenzhu Guo¹, Yuliu¹, Jianping Liang¹

Affiliations

¹ Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmacceutical Development, Ministry of Agriculture, Lanzhou Institute of Animal Science and Veterinary Pharmaceutics Science, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.
² University Hospital of Gansu Traditional Chinese Medicine, Lanzhou, Gansu, China.
³ Université Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, CNRS, Paris, France.

Abstract

Novel pleuromutilin derivatives designed based on the structure of valnemulin were synthesized and evaluated for their in vitro antibacterial activities. These pleuromutilin derivatives with substituted amino moiety exhibited excellent activities against methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Escherichia coli, and Streptococcus agalactiae. Compound 5b showed the highest antibacterial activities and even exceeded tiamulin. Moreover, the docking experiments provided information about the binding model between the synthesized compounds and peptidyl transferase center (PTC) of 23S rRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amines / chemistry*
Binding Sites
Crystallography, X-Ray
Diterpenes / chemical synthesis
Diterpenes / chemistry
Diterpenes / pharmacology
Escherichia coli / drug effects
Methicillin-Resistant Staphylococcus aureus / drug effects
Microbial Sensitivity Tests
Molecular Docking Simulation
Pleuromutilins
Polycyclic Compounds
Staphylococcus epidermidis / drug effects
Streptococcus agalactiae / drug effects

Substances

Amines
Diterpenes
Polycyclic Compounds

Grants and funding

This work was supported by Basic Scientific Research Funds in Central Agricultral Scientific Research Institutions (number 1610322013004) and “Five-Year” plan of national science and technology projects in rural areas (number 2011AA10A214). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.