New chalcone derivatives: synthesis, antiviral activity and mechanism of action

In this work, twenty-eight chalcone derivatives containing a purine (sulfur) ether moiety were synthesized and their antiviral activities were evaluated. Biological results showed that compound5dexhibited outstanding inactive activity against tobacco mosaic virus (TMV)in vivo(EC50= 65.8 mu g mL(-1)), which is significantly superior to that of ribavirin (EC50= 154.3 mu g mL(-1)). Transmission electron microscopy indicated that compound5dcan break the integrity of TMV particles. The results of microscale thermophoresis, fluorescence titration and molecular docking showed that compound5dhad stronger combining affinity (K-a= 1.02 x10(5)L mol(-1),K-d= 13.4 mu mol L-1) with TMV coat protein (TMV-CP), which is due to the formation of five hydrogen bonds between compound5dand the amino-acid residues of TMV-CP. These findings revealed that compound5dcan effectively inhibit the infective ability of TMV. This work provides inspiration and reference for the discovery of new antiviral agents.