Novel flavonoid derivatives containing benzothiazole as potential antiviral agents: design, synthesis, and biological evaluation

Abstract

A series of flavonol derivatives containing benzothiazole were designed and synthesized. The structures of all the compounds were characterized by NMR and HRMS. The results of the bioactivity assay showed that some of the target compounds possessed outstanding in vivo antiviral activity against the tobacco mosaic virus (TMV). Among them, the median effective concentration (EC50) of L20 was 90.5 µg/mL for curative activities against TMV, which was better than that of ningnanmycin (NNM: 252.0 µg/mL). The microcalorimetric thermophoresis (MST) and molecular docking experiments showed that L20 had a strong binding ability with TMV-CP; the malondialdehyde (MDA) and superoxide dismutase assay (SOD) activity measurements also fully confirmed that L20 stimulated the plant immune system and strengthened the plant's resistance to diseases by lowering the MDA content and increasing the SOD activity. In addition, the chlorophyll content test experiment found that L20 could reduce the destructive effect of viruses on chloroplasts, increase the content of chlorophyll, and promote photosynthesis. In conclusion, above experimental results suggested that flavonol derivatives containing benzothiazole could be further investigated as new plant virus antiviral drugs.