Synthesis and biological activity of hydroxycinnamoylcontaining antiviral drugs

Abstract

Seven N-hydroxycinnamoyl amides were synthesized by 1-[3-(dimethylamino) propyl]-3-ethylcarbodiimide/1-hydroxybenzotriazole (EDC/HOBt) coupling of the corresponding substituted cinnamic acids (p-coumaric-, ferulic-, sinapic- and caffeic acids) with influenza antivirals (amantadine, rimantadine and oseltamivir). The 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 a catechol moiety, exhibited the most potent DPPH radical-scavenging activity. Amide (1) also displayed tyrosinase inhibitory effect toward L-tyrosine as the substrate (=50 %). The synthesized compounds were also investigated for their in vitro inhibitory activity against the replication of influenza virus A (H3N2). © 2014 SCS. All rights reserved.