Myricetin derivatives containing the benzoxazinone moiety discovered as potential anti-tobacco mosaic virus agents

Abstract

A series of myricetin derivatives containing benzoxazinone were designed and synthesized. The structures of all compounds were characterized by NMR and HRMS. The structure of Y4 had been confirmed by single-crystal X-ray diffraction analysis. The test results of EC₅₀ values of tobacco mosaic virus (TMV) suggested that Y8 had the best curative and protective effects, with EC₅₀ values of 236.8, 206.0 μg/mL, respectively, which were higher than that of ningnanmycin (372.4, 360.6 μg/mL). Microscale thermophoresis (MST) experiments demonstrated that Y8 possessed a strong binding affinity for tobacco mosaic virus coat protein (TMV-CP), with a dissociation constant (K_d) value of 0.045 μM, which was superior to the ningnanmycin (0.700 μM). The findings of molecular docking studies revealed that Y8 interacted with multiple amino acid residues of TMV-CP through the formation of non-covalent bonds, which had an effect on the self-assembly of TMV particles. The malondialdehyde (MDA) and superoxide dismutase assay (SOD) content assays also fully verified that Y8 could stimulate the plant immune system and enhance disease resistance by reducing MDA content and increasing SOD content. In summary, myricetin derivatives containing benzoxazinone could be considered to further research and development as novel antiviral agents.

Keywords: Antiviral activity; Benzoxazinone; Mechanism of action; Myricetin.