Design, synthesis and anti-TMV activity study of flavonol derivatives containing pyrimidine

A series of flavonol derivatives containing pyrimidine moieties were designed and synthesized, and their anti-tobacco mosaic virus (TMV) activities were systematically evaluated. The half-maximal effective concentration (EC50) values of these compounds were determined. The results revealed that P6 exhibited superior curative activity (EC₅₀ = 100.2 μg mL−1) and protective activity (EC₅₀ = 136.0 μg mL−1) compared to the positive control ningnanmycin (NNM; EC₅₀ = 236.4 and 235.9 μg mL−1, respectively). Transmission electron microscopy (TEM) analysis demonstrated that P6 effectively disrupted TMV particle morphology. Additionally, Microscale thermophoresis (MST), molecular docking studies and molecular dynamics confirmed the strong binding affinity between P6(Kd = 0.0853) and tobacco mosaic virus coat protein (TMV-CP). Furthermore, P6 significantly enhanced superoxide dismutase (SOD) activity (In the P6 + TMV group, SOD activity increased rapidly from 1 to 5 d, peaked on 5 d, and declined slightly by 7 d) and chlorophyll content (in P6-treated leaves, chlorophyll content increased within 1–3 d, peaked on 3 d, and then decreased slightly) in tobacco leaves. These findings suggest that this series of compounds possesses promising potential as antiviral agents.