Synthesis And Biological Activity Of Chalcone Derivatives Containing Pyrimidine Or Triazolothiadiazol

Chalcone is a kind of natural flavonoids widely found in nature.A large number of studies have shown that chalcone derivatives have broad-spectrum physiological and pharmacological activities such as antibacterial and antiviral activities,which have become a research hotspot in the creation of new pesticides.Therefore,it is of great feasibility to develop a chalcone derivative with low toxicity,high efficiency,unique mode of action and broad-spectrum biological activity based on the structure of chalcone.In order to study new fungicides and antiviral agents,chalcone was used as the lead compound in this paper.Pyrimidine and triazolothiadiazole were introduced into chalcone structure by active splicing method,and 23 chalcone derivatives T1-T23containing pyrimidine and 39 chalcone derivatives L1-L39 containing triazolothiadiazole were synthesized.The structures of all derivatives were characterized by ¹H NMR,¹³C NMR,¹⁹F NMR and HRMS,and their antibacterial and antiviral activities were tested.The main research contents of this paper are summarized as follows:1.Twenty-three chalcone derivatives containing pyrimidine were designed and synthesized.The inhibitory activity of these derivatives against tobacco mosaic virus（TMV）was tested by half leaf spot method with Ningnanmycin as the control agent.The results showed that most of the target compounds exhibited better anti-TMV activity than ningnanmycin at 500μg/m L.The EC₅₀ values of T1,T7,T9 and T19 were219.2,228.2,279.9 and 234.9μg/m L,respectively,which were better than that of Ningnanmycin（320.1μg/m L）.The EC₅₀ values of compounds T5,T9,T19 and T23were 235.0,220.0,199.5 and 187.2μg/m L,respectively,which were better than that of Ningnanmycin（307.4μg/m L）.The mechanism of T19 and TMV coat protein（TMV-CP）was preliminarily explored by microthermophoresis（MST）and molecular docking.The results showed that T19 had a strong binding affinity for TMV coat protein,and its dissociation constant（Kd）was 0.00310±0.000916μM,which was better than that of Ningnanmycin（0.165±0.0799μM）.2.Thirty-nine chalcone derivatives containing triazolothiadiazole were designed and synthesized.The antifungal activities of these derivatives were tested by mycelium growth rate method with azoxystrobin as control.The results showed that some compounds showed good antibacterial activity at 100μg/m L.The inhibition rates of compounds L31 and L32 against Phomopsis were 64%-73%,which were better than that of the control fungicide azoxystrobin（56%）.The EC₅₀values of the above compounds were tested.The results showed that the EC₅₀ values of compounds L31and L32 against Phomopsis were 15.9 and 44.2μg/m L,respectively,which were better than the control fungicide azoxystrobin（69.4μg/m L）.In addition,the mechanism of action of compound L31 showed that the compound could affect mycelial growth by destroying the cell membrane integrity of Phomopsis sp.and the higher the concentration of the compound,the greater the degree of damage to membrane integrity.