Study On Synthesis And Biological Activity Of Myricetin Derivatives Containing Azole Or Chalcone

Myricetin,as a kind of polyhydroxy flavonoid compound,has aroused widespread concern owing to its extensive biological properties of antibacterial,antiviral,anticancer,anti-inflammatory and anti-oxidative activities.In this paper,1,3,4-thiadiazole myricetin derivatives A series（A1-A16）and myricetin chalcone derivatives B series（B1-B18）was designed and synthesized with the myricetin as lead compound.The target compounds were characterized by ¹H NMR,¹³C NMR and HRMS,the antibacterial,antiviral and antitumor activities were tested.Antibacterial activity of the target compounds were tested by turbidity method,the experimental results showed that most of the target compounds possessed good inhibitory activity against X.citri and X.oryzae.The EC₅₀ values of compounds A1,A6-9,A12,B1,B6-9 and B12 against X.citri were superior to those of Bismerthiazol（34.7μg/mL）,the values of compounds A7,A9,and B6 against X.citri were 11.5,18.9,and19.9μg/mL,respectively.The EC₅₀ values of compounds A5,A6,A9,B6 and B15 against X.oryzae were better than that of Bismerthiazol（45.3μg/mL）,the values of compounds A1,A3,A5,A9,B1,B5 and B6 against R.solanacearum were better than that of Bismerthiazol（67.2μg/mL）.Anti-plant viral activity of the targets compounds were tested by half-leaf method,the results showed that the inhibitory rate of compounds A₇,A₁₂,B₃,B_7-9,B₃ and B₁₂against TMV were higher than that of Ribavirin（40.6%）and close to Ninnanmycin（52.7%）with the test concentration of 500μg/mL.The therapeutic activity inhibition rate against TMV of compounds A7,A10,B3,B7,B8,B11-13,B15 and B17 were higher than that of Ribavirin（51.1%）.The protective activity against TMV of compound B8was 65.8%,which was close to that of Ninnanmycin（66.0%）.The passivation activity of most of the compounds against TMV were superior to that of Ribavirin（71.1%）,and the passivation activity against TVM of compound B7 reached 80.2%.Anti-tumor activity of some target compounds were tested by MTT colorimetry method with the Gemcitabine as positive control agent.The experimental results showed that most of the myricetin derivatives have significant inhibitory effect on SMMC-7721 cells for 72 h,and the inhibitory effect of most of the compounds exceeded the parental structure myricetin both at low and high concentrations.The inhibitory effect of compound A13 with the concenration of 10μM on hepatoma SMMC-7721 cells had the most obvious inhibitory activity of 86.23%,which was far more than the same concentration of control drug Gemcitabine（42.52%）.