Design, synthesis, and antiviral activities of myricetin derivatives containing phenoxypyridine

A series of myricetin derivatives containing phenoxypyridine structure were designed and synthesized on the basis of the natural product myricitrin, which were structurally characterized on NMR and HRMS. The results of antiviral activity tests showed that some of the target compounds exhibited better inhibitory effects. Among them, B19 and B21 showed better curative activity with EC50 values of 195.67 and 173.64 mu g/mL, respectively, which were superior to that of the control agent ningnanmycin(NNM) (238.30 mu g/mL). B21 showed better protective activity with EC50 value of 236.37 mu g/mL, which was better than that of the control agent NNM (269.89 mu g/mL). The results of microcalorimetry showed that B1, B19 and B21 had good binding affinity with tobacco mosaic virus capsid protein (TMV-CP), and the Kd values were 0.059, 0.093 and 0.069 mu M, which was higher than that of NNM (Kd = 2.78 mu M). The molecular docking results showed that the hydrogen bond lengths between B1, B21 and the key amino acid residues of TMV-CP were shorter and with more tightly bound than those of NNM. In B21-treated tobacco leaves, chlorophyll content and superoxide dismutase (SOD) activity were significantly elevated, indicating that B21 can participate in regulating plant photosynthesis as well as defense enzymes and inducing plants to improve disease resistance.