Reaction of rosmarinic acid with nitrite ions in acidic conditions: discovery of nitro- and dinitrorosmarinic acids as new anti-HIV-1 agents

J Med Chem. 2008 Apr 24;51(8):2575-9. doi: 10.1021/jm7011134. Epub 2008 Mar 20.

Abstract

Rosmarinic acid was reacted with nitrite ions under acidic conditions to give 6'-nitro- and 6',6''-dinitrorosmarinic acids according to the reaction time. Both compounds were active as HIV-1 integrase inhibitors at the submicromolar level. They also inhibited the viral replication in MT-4 cells with modest and similar selectivity indexes. The nitration of rosmarinic acid strongly improves the anti-integrase inhibition and the antiviral activity without increasing the cellular toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids / chemistry
  • Base Sequence
  • Cell Line
  • Cinnamates / chemistry*
  • Cinnamates / pharmacology*
  • DNA Primers
  • Depsides / chemistry*
  • Depsides / pharmacology*
  • HIV Integrase Inhibitors / chemistry*
  • HIV Integrase Inhibitors / pharmacology*
  • HIV-1 / drug effects*
  • Humans
  • Hydrogen-Ion Concentration
  • Mass Spectrometry
  • Microbial Sensitivity Tests
  • Nitrites / chemistry*
  • Rosmarinic Acid
  • Spectrophotometry, Ultraviolet

Substances

  • Acids
  • Cinnamates
  • DNA Primers
  • Depsides
  • HIV Integrase Inhibitors
  • Nitrites