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

Abstract

26 derivatives of myricetin containing pyridazinone were designed and synthesized from the natural product myricitrin, which were structurally characterized by nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HRMS), and the structure of A14 was further determined using an X-ray single crystal diffractometer. The in vivo anti-tobacco mosaic virus (TMV) activity was tested by the half-leaf method, and the results showed that A4, A23 and A26 possessed better curative activity with effective concentration 50% (EC₅₀) of 131.6, 138.5 and 118.9 μg mL⁻¹, which were superior to that of ningnanmycin (NNM) (235.6 μg mL⁻¹), respectively. A24 and A26 possessed better protective activity with EC₅₀ values of 117.4 and 162.5 μg mL⁻¹, superior to that of NNM (263.2 μg mL⁻¹). Microcalorimetric thermophoresis (MST) and molecular docking assays showed that A23 and A26 had strong binding ability with TMV-CP. After treatment with A26, the chlorophyll content in tobacco was significantly higher than that in the control group, and the growth rate of malondialdehyde content was slowed down. This further confirmed that the drug molecules have good antiviral activity.