Synthesis and biological activity of hydroxycinnamoyl containing antiviral drugs

Abstract

Seven N-hydroxycinnamoyl amides were synthesized by EDC/HOBt coupling of the corresponding substituted cinnamic acids (p-coumaric-, ferulic-, sinapic- and caffeic acids) with influenza antivirals (amantadine, rimantadine and oseltamivir). DPPH (1,1-diphenyl-2-picrylhydrazyl) scavenging abilities and the inhibitory effect on mushroom tyrosinase activity (using L-tyrosine as the substrate) were investigated in vitro. Amongst the synthesized compounds, N-[(E)-3-(3’,4’-dihydroxyphenyl)-2-propenoyl]oseltamivir (1) and N-[(E)-3-(3’,4’-dihydroxyphenyl)-2-propenoyl]rimantadine (4), containing catechol moiety, exhibited the most potent DPPH radical-scavenging activity. Amide (1) displayed also tyrosinase inhibitory effect toward L-tyrosine as the substrate (~50%). Due to its biological activities revealed so far compound (1) can be considered as a promising candidate for a cosmetic ingredient. The synthesized compounds were also investigated for their in vitro inhibitory activity against the replication of influenza virus A (H3N2).

Keywords

• N-hydroxycinnamoylamides
• influenza antivirals
• mushroom tyrosinase
• monophenolase activity
• antioxidant activity
• anti-influenza activity