Synthesis, configurational analysis and antiviral activities of novel diphenylacrylic acids with caffeic acid as the lead compound

Abstract

A series of novel caffeic acid derivatives with the core structure of diphenylacrylic acids were designed and synthesized. The 24 compounds involved were confirmed by NMR spectra (1H NMR, 13C NMR, HMQC or HMBC) and evaluated for their antiviral activities against RSV, HSV-1 and EV71. These derivatives exist as (E)- or (Z)- isomers of diphenylacrylic acid, and the configurational analysis method was illustrated by 1H NMR for the first time. The potential A2 showed a selective effect against HSV-1 but a weak effect against RSV and EV71 with a therapeutic index (TI) of 32, which was significantly better than ribavirin and caffeic acid. Beside, the A2 had an obvious scavenging effect on DPPH• and ABTS•+ and showed a protective effect against oxidative damage of hepatocyte L02 cells. In addition, molecular docking studies showed that A2 had a better binding affinity to the HSV-1 target compared with caffeic acid. Therefore, the A2 is worthy of being further screened as a lead compound and investigated for its mechanism of inhibiting HSV-1.