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.

设计合成了一系列以二苯基丙烯酸为核心结构的新型咖啡酸衍生物。所涉及的24种化合物均通过NMR谱（¹ H NMR、¹³ C NMR、HMQC或HMBC）进行了确认，并评估了它们对RSV、HSV-1和EV71的抗病毒活性。这些衍生物以二苯基丙烯酸的( E )-或( Z )-异构体存在，并且首次通过^{1 H NMR阐明了构型分析方法。}潜在的A2对HSV-1表现出选择性作用，但对RSV和EV71作用较弱，治疗指数（TI）为32，明显优于利巴韦林和咖啡酸。此外，A2对DPPH•和ABTS•有明显的清除作用。⁺并对肝细胞L02细胞的氧化损伤显示出保护作用。此外，分子对接研究表明，与咖啡酸相比，A2 对 HSV-1 靶点具有更好的结合亲和力。因此，A2值得作为先导化合物进一步筛选并研究其抑制HSV-1的机制。