Evaluation of neomycin analogues for HIV-1 RRE RNA recognition identifies enhanced activity simplified neamine analogues

Bioorg Med Chem Lett. 2019 Jan 15;29(2):339-341. doi: 10.1016/j.bmcl.2018.11.004. Epub 2018 Nov 9.

Abstract

Synthetic neamine mimetics have been evaluated for binding to the HIV-1 Rev response element. Modified neamine derivatives, obtained from reductive amination of neamine, led to identification of new 6-amino modified neamine-type ligands with HIV-1 RRE binding affinity up to 20× that of neamine and up to 6× that of the more complex neomycin itself. This provides a noteworthy structure-activity increase and a useful lead to simplified, chemically accessible mimetics.

Keywords: Aminoglycosides; HIV-1; Neamine; Neomycin; RNA RRE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Framycetin / chemical synthesis
  • Framycetin / chemistry
  • Framycetin / pharmacology*
  • HIV-1 / drug effects*
  • Molecular Structure
  • Neomycin / analogs & derivatives
  • Neomycin / chemistry
  • Neomycin / pharmacology*
  • RNA, Viral / drug effects*
  • Response Elements / drug effects*
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • RNA, Viral
  • Framycetin
  • neamine
  • Neomycin