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.
Mélanie Dubois  1 ,  Fabrice Bailly ,  Gladys Mbemba ,  Jean-François Mouscadet ,  Zeger Debyser ,  Myriam Witvrouw ,  Philippe Cotelle
Affiliations
  • 1. Laboratoire de Chimie Organique et Macromoléculaire, UMR CNRS 8009, Université de Lille 1, 59655 Villeneuve d'Ascq, France.
PMID: 18351727 DOI: 10.1021/jm7011134
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.