Reaction of rosmarinic acid with nitrite ions in acidic conditions: discovery of nitro- and dinitrorosmarinic acids as new anti-HIV-1 agents.
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.
Dubois
Mélanie
M
Laboratoire de Chimie Organique et Macromoléculaire, UMR CNRS 8009, Université de Lille 1, 59655 Villeneuve d'Ascq, France.
Bailly
Fabrice
F
Mbemba
Gladys
G
Mouscadet
Jean-François
JF
Debyser
Zeger
Z
Witvrouw
Myriam
M
Cotelle
Philippe
P
D000143:Acids / Q000737:chemistry; D001483:Base Sequence; D002460:Cell Line; D002934:Cinnamates / Q000737:chemistry* / Q000494:pharmacology*; D017931:DNA Primers; D053630:Depsides / Q000737:chemistry* / Q000494:pharmacology*; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D009573:Nitrites / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D000097123:Rosmarinic Acid
D000143:Acids; D002934:Cinnamates; D017931:DNA Primers; D053630:Depsides; D019428:HIV Integrase Inhibitors; D009573:Nitrites; D000097123:Rosmarinic Acid