Synthesis And Biological Activity Of Myricetin Derivatives Containing Benzimidazole

Myricetin compounds,as an important flavonoid derivative,have a variety of biological activities such as antibacterial,antiviral,antitumor,anti-glycemic and anti-inflammatory.In recent years,studies have found that such compounds have obvious antibacterial and antiviral activity.At the same time,benzimidazole is an important heterocyclic compound,which has excellent bactericidal activity and also has various biological activities such as antiviral and antitumor.At present,some derivatives containing benzimidazole have been used for clinical treatment,this article uses the principle of active splicing to introduce benzimidazole into the myricetin structure,and synthesize 42 myricetin derivatives containing benzimidazole.Compounds are processed by ¹H NMR,¹³C NMR,¹⁹F NMR and HRMS characterization.The compounds were tested for their anti-plant pathogens and antiviral activity.At the same time,the crystal structures of compounds 4g and 6n were determined by a single crystal diffractometer to further confirm the structure of the series of compounds.The antibacterial activities of the target compounds against plant pathogens were tested in vitro by the turbidimeter test.The commercial bactericides thiodiazole copper（TC）and bismerthiazol（BT）were chosen as control.The experimental results showed that the EC₅₀values of compounds 4l,4o,4t,6a,6i and 6k against Xanthomonas axonopodis pv.citri（Xac）were 14.4,19.1,21.3,27.8,24.2 and 20.0μg/m L,respectively,which were better than the control TC（69.5μg/m L）and BT（89.5μg/m L）.The EC₅₀values of compounds 4l,4p,4u,6a,6d and 6e against Ralstonia solanacearum（Rs）were 10.5,18.1,11.5,22.0,21.7 and 14.5μg/m L,respectively,which is better than the control TC（118.9μg/m L）and BT（55.1μg/m L）.The EC₅₀values of compounds 4k,4l,4m,4q,6d,6i and 6r on Xanthomonas oryzae pv.oryzae（Xoo）were 14.0,17.2,17.2,8.2,20.4,24.9 and 36.1μg/m L,respectively,which were better than the control TC（83.1μg/m L）and BT（60.1μg/m L）.At the same time,the target compound 4q was subjected to in vivo experiments on Xoo using the shearing leaf comparison method.The results showed that in terms of curative activity,the control effect of compound 4q was（45.2%）,which was better than the control TC（30.5%）and BT（34.8%）.In terms of protective activity,the control effect of compound 4q was（48.6%）,which was better than the control TC（35.7%）and BT（41.8%）.Scanning electron microscopy experiments showed that the antibacterial effect of compound 4q on Xoo caused the bacterial cell membrane to wrinkle and break.The curative,protective and inactivation activities against tobacco mosaic virus（TMV）in vivo at 500μg/m L were assessed by the half leaf blight spot method.The commercial agent ningnanmycin was used as control.Compound 6n have a better curative activity on TMV,with corresponding inhibition rate is 54.1%,which was better than ningnanmycin（49.0%）.In addtion,compounds 6j and 6n exhibited signifcant protective effects against TMV,with corresponding inhibitory rates of 61.5and 57.6%,respectively,which were superior to that of ningnanmycin（55.8%）.Microscale thermophoresis（MST）also showed that the binding of compound 6n to TMV coat protein（TMV-CP）gave a K_dvalue of 1.049±0.582μmol/L,which was superior to the lead compound myricetin（67.269±27.940μmol/L）and the control agent ningnanmycin（1.058±0.285μmol/L）,It shows that there is a strong interaction between compound 6n to TMV-CP.