Synthesis And Biological Activity Of Myricetin Derivatives Containing Triazolothiadiazole Or Sulfide Quinolin

Myricetin,a flavonoid compound,exists widely in nature and has extensive and significant biological activities such as antiviral,antibacterial,anticancer and anti-inflammatory.1,2,4-triazole[3,4-b]-1,3,4-thiadiazole,as a class of thiadiazole derivatives,also showed good biological activity,mainly reflected in the medical antibacterial drugs and antibacterial drugs;Meanwhile,quinoline is a kind of alkaloid with natural activity,which has been widely concerned because of its good antibacterial effect,anti-tuberculosis,anti-cancer and other biological activities.As a substitute methylene group,thioether structure has the characteristics of high efficiency and low toxicity,and is often used as an effective active group in the development of pesticides.In this paper,myricetin derivatives containing 1,2,4-triazole[3,4-b]-1,3,4-thiadiazole and thio-quinoline were synthesized by introducing the lead compound myricetin with1,2,4-triazole[3,4-b]-1,3,4-thiadiazole and thio-quinoline as active groups.All the target compounds were characterized by ¹H NMR,¹³C NMR and HRMS.The crystal structures of compounds A5 and B4 were determined by single crystal X-ray diffractometer.The bacteriostatic,fungicidal and antiviral biological activities of all the target compounds were tested,and the preliminary mechanism studies were conducted.Turbidimetric method was used to test the positive control of TC,BT and the lead compound myricetrin at concentrations of 100 and 50μg/m L.The results were as follows:When the concentration was 100μg/m L,the inhibition rates of compounds A15 and A16 against Xac were 63.3 and 54.7%,which were close to the commercial control agent BT（53.1%）and TC（57.3%）.The inhibition rate of compound A15against Xoo（59.9%）was close to that of commercial control agent BT（59.5%）and TC（62.3%）.The inhibition rate of compound A16 against Psa was 51.1%,close to that of control agent BT（50.3%）and TC（55.9%）.When the concentration was 50μg/m L,the inhibition rate of compound A8 on Xac was 39.0%,which was close to that of commercial control agent BT（36.1%）and TC（40.1%）,and the inhibition rate of compound A16 on Psa was 41.8%,which was close to that of commercial control agent BT（34.8%）and TC（37.8%）.Half leaf spot method was used,with ningnanmycin and myricetrin as positive controls.The results showed that:The EC₅₀ values of the anti-TMV curative activities of compounds A5,A8,A9,B14,B28 and B30 against tobacco mosaic virus（TMV）were 88.3,139.1,109.9,143.1,141.7 and 80.1μg/m L,respectively,which were better than the commercial drug ningnanmycin（227.2μg/m L）.The EC₅₀ values of the anti-TMV protective activities of compounds A15,A16,B6,B13 and B24 were 86.3,79.2,86.5,95.3 and 89.6μg/m L,respectively,which were better than the commercial drug ningnanmycin（179.2μg/m L）.In addition,the interaction of A12,A16,B6,B13,myricetrin and ningnanmycin with tobacco mosaic virus coat protein（TMV CP）was further investigated by microscale thermophoresis（MST）.The K_d values of compounds A12,A16,B6,B13 and TMV CP were 0.015,0.056,0.013,0.344μmol/L,respectively.They were superior to myricetrin（61.447μmol/L）and ningnanmycin（3.215μmol/L）,indicating that the binding ability of compounds A12,A16,B6,B13 was stronger than myricetin and ningnanmycin.