Rigid spiroethers targeting the decoding center of the bacterial ribosome

Bioorg Med Chem. 2014 Feb 15;22(4):1329-41. doi: 10.1016/j.bmc.2013.12.068. Epub 2014 Jan 10.

Abstract

Continuing our efforts towards understanding the principles governing ribosomal recognition and function, we have synthesized and evaluated a series of diversely functionalized 5,6-, 6,6- and 7,6-spiroethers. These compounds successfully mimic natural aminoglycosides regarding their binding to the decoding center of the bacterial ribosome. Their potential to inhibit prokaryotic protein production in vitro along with their antibacterial potencies have also been examined.

Keywords: Aminoglycosides; Antibacterials; RNA recognition; Ribosomal A-site; Spiroethers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Binding Sites
  • Ethers, Cyclic / chemical synthesis
  • Ethers, Cyclic / chemistry*
  • Ethers, Cyclic / pharmacology
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • Microbial Sensitivity Tests
  • Molecular Dynamics Simulation
  • Protein Structure, Tertiary
  • RNA, Ribosomal, 16S / chemistry
  • RNA, Ribosomal, 16S / metabolism
  • Ribosomes / chemistry
  • Ribosomes / metabolism*
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / chemistry*
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Ethers, Cyclic
  • RNA, Ribosomal, 16S
  • Spiro Compounds
  • spiroether