Antiviral activity evaluation and action mechanism of chalcone derivatives containing phenoxypyridine

In this paper, a series of phenoxypyridine-containing chalcone derivatives (L1-L28) were designed and synthesized, characterized on NMR and HRMS. Ningnanmycin (NNM) was used as a control agent. The results of the antiviral activity testing showed that the curative activity EC₅₀ values of L1 and L4 against TMV were 140.5 and 90.7 μg/mL, respectively, which were superior to that of NNM (148.3 μg/mL). The EC₅₀ values of 154.1, 102.6 and 140.0 μg/mL for the anti-TMV protective activities of L1, L4 and L15 were superior to that of NNM (188.2 μg/mL). The mechanism of action between L4 and NNM and tobacco mosaic virus capsid protein (TMV-CP) was preliminarily investigated. The results of microscale thermophoresis (MST) experiments showed that L4 had a strong binding affinity for TMV-CP with a dissociation constant Kd value of 0.00149 µM, which was better than that of NNM (2.73016 µM). The results of molecular docking experiments showed that L4 formed shorter hydrogen bonds with amino acid residues of TMV-CP than NNM and formed more amino acid residues than NNM, which indicated that L4 was more tightly bound to TMV-CP. This study suggested that phenoxypyridine-containing chalcone derivatives can be used as new anti-TMV drugs through further research and development.