Synthesis of novel pleuromutilin derivatives. Part 1: preliminary studies of antituberculosis activity

Bioorg Med Chem Lett. 2015 Apr 15;25(8):1799-1803. doi: 10.1016/j.bmcl.2015.02.023. Epub 2015 Feb 17.

Abstract

The worldwide threat from tuberculosis (TB) has resulted in great demand for new drugs, particularly those that can treat multidrug-resistant TB. We synthesized novel pleuromutilin derivatives with N-benzylamine side chain substituted at the C14 position and evaluated their activity in vitro against a virulent strain of Mycobacterium tuberculosis (H37Rv). The primary assay results showed that five compounds inhibited the H37Rv at 20μM, with a MIC of one of the analogues as low as 7.2μM.

Keywords: Antitubercular activity; N-Benzylamine side chain; Pleuromutilin derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / chemical synthesis*
  • Antitubercular Agents / chemistry
  • Antitubercular Agents / pharmacology
  • Diterpenes / chemical synthesis
  • Diterpenes / chemistry
  • Diterpenes / pharmacology
  • Drug Design
  • Drug Resistance, Microbial
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects
  • Pleuromutilins
  • Polycyclic Compounds
  • Structure-Activity Relationship

Substances

  • Antitubercular Agents
  • Diterpenes
  • Polycyclic Compounds