Synthesis And Biological Evaluation Of 1,2,3-Triazole Derivaties

1,2,3-triazole derivaties have a broad spectrum of biological activities,including antibacterial,anti-inflammatory,anti-HIV,anti-tubercular,anti-cancer,anti-alpha-glycosidase and antifungal activities,some of them are widely used in the field of pharmaceutical chemistry.A total of 89 1,2,3-triazole derivatives including hydrazide,oxime ether,acylhydrazone and amide were synthesized based on the aryl azides,79 of them were first reported.Spectroscopy methods were used to confirm their structure.The antifungal activities were evaluated against different phytopathogenic fungi in vitro and in vivo.Concrete research content were as follows:In the first part,1,2,3-triazole hydrazide,oxime ether,acylhydrazone and amide derivatives were designed and synthesized based on the 1,2,3-triazole phenylhydrazone,which were proved to have good significant antifungal activities in our previous work.Their structures were determined based on 1H-NMR spectroscopy,MS,elemental analysis.The antifungal activities were evaluated against four phytopathogenic fungi including Rhizoctonia solani,Sclerotinia sclerotiorum,Fusarium graminearum and Magnaporthe oryza using mycelium growth inhibition method in vitro.Compound 6ad exhibited the most potent anti-phytopathogenie activity,with ECso values of 0.18,0.35,0.37 and 2.25?g·mL-1 respectively.The in vivo protective effect of 6ad against rice sheath blight could reach 55.9%,at a concentration of 100 ?g·mL-1,higher than Valiidamycin A(43.3%).Treatment with 100 ?g·mL-1 of 6ad against rice blast resulted in 63.3%,Carbendazim was 88.0%at the 50?g·mL-1,and conidia of M.oryza could not form the germ tube and appressorium germinate at a concentration of 1?g·mL-1.Systemic translation of 6ad in wheat leaves showed good upward transportation.The field effect of 6ad against fusarium head blight could reach 58.76%at 20 a.i.g/m,higher than Carbendazim(48.30 at 40 a.i.g/m).In the second part,with the Boscalid as lead compound,we introduced 1,2,3-triazole into the location of biphenyl to designe and synthesize 56 derivatives,53 of them were first reported.Their structures were determined based on 1H-NMR spectroscopy,MS,elemental analysis,and X-ray single-crystal diffraction was also applied to confirm the crystal structures of A1-1 and B5-1.The antifungal activities were evaluated against Fusarium solani,Botrytis cinerea,Rhizoctonia cerealis,Gaeu-mannomyces graminsis,S.sclerotiorum,Alternaria solani,Colletotrichum orbiculare,Fusarium moniliforme,Phytophthora capsici at 50 ?g·mL-1,compound A4-3 exhibited best antifungal activities,with EC50 values of 8.75,1.76,5.30,1.08 ?g·mL-1 against B.cinerea,R.cerealis,G graminsis and S.sclerotiorum respectively.In vivo test demonstrated that A4-3 was effective in control of rape sclerotinia rot,B.cinerea and wheat powdery mildew.In addition,inhibition activities against SQR were tested and the result proved the effectiveness of targets design in the enzyme level.Finally,molecular docking were used by DS and SYBYL to study the complex of A4-3 and the target protein 2FBW,the result showed amino acid residues of recepter interacted with A4-3 by many bonging such as hydrogen bonding and hydrophobic interaction.