Antiviral activity evaluation and action mechanism of myricetin derivatives containing thioether quinoline moiety

A variety of myricetin derivatives containing thioether quinoline moiety were designed and synthesized. Their structures of title compounds were determined by 1 H NMR, 13 C NMR, 19 F NMR, and HRMS. Single-crystal X -ray diffraction experiments were carried out with B4 . Antiviral activity indicated that some of the target compounds exhibited remarkable anti-tobacco mosaic virus (TMV) activity. In particular, compound B6 possessed significant activity. The half maximal effective concentration (EC 50 ) value of the curative activity of compound B6 was 169.0 μg/mL, which was superior to the control agent ningnanmycin (227.2 μg/mL). Meanwhile, the EC 50 value of the protective activity of compound B6 was 86.5 μg/mL, which was better than ningnanmycin (179.2 μg/mL). Microscale thermophoresis (MST) indicated that compound B6 had a strong binding capability to the tobacco mosaic virus coat protein (TMV-CP) with a dissociation constant ( K d ) value of 0.013 μmol/L, which was superior to that of myricitrin (61.447 μmol/L) and ningnanmycin (3.215 μmol/L). And the molecular docking studies were consistent with the experimental results. Therefore, these novel myricetin derivatives containing thioether quinoline moiety could become potential alternative templates for novel antiviral agents. Graphical abstract