Synthesis And Biological Evaluation Of 1,2,3-triazole Derivaties As Fungicides

1,2,3-triazole derivaties are associated with a broad spectrum of biological activities,including antibacterial,anti-tubercular,anti-HIV,anti-alpha-glycosidase and antifungal activities,some of them playing key roles in new drug research.Copper catalytic azide and terminal alkyne cycloaddition reaction namely "click chemistry" give a new and convenient way to 1,4-di-substituted-1,2,3-triazoles.46 substituted phenylhydrazone and carbohydrazide 1,2,3-triazoles were synthesized,44 of them were first reported.Spectroscopy methods were used to confirm their structure.Their antifungal activities were evaluated against different phytopathogenic fungi,several compounds show good in vivo activities.The results of this study provide important clues for new type of chemical pesticide research,concrete research content were as follows:Phenylhydrazone derivaties show good antifungal activities.In part one,a series of substituted 1,2,3-triazoles were synthesized as scaffold via Click chemistry.Substituted phenylhydrazone groups were linked to the 1,2,3-triazole scaffold to 26 compounds?5a-5z?.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 structure of 51.The antifungal activities were evaluated against three phytopathogenic fungi including Rhizoctonia solani,Sclerotinia sclerotiorum,Fusarium graminearum and one phytopathogenic oomycetes Phytophthora capsici,by mycelium growth inhibition method in vitro.Compound 5p exhibited significant anti-phytopathogenic activity,with the EC50 values of 0.18,2.28,1.01,and 1.85 ?g·mL^-1,respectively.In vivo test demonstrated that 5p was effective in control of rice sheath blight,rape sclerotinia rot and fusarium head blight.Based on the antigungal data of R.solani,3D-QSAR model was built for a systematic SAR profile to explore more potent 1,2,3-triazole phenylhydrazone analogs as novel fungicides.The in vivo protective effect of 5p against RSB could reach 90.1%,at a concentration of 100 ?g·mL^-1,which was significantly higher than that of Validamycin A?wp?which was 50.0%;Treatment with 250 ?g·mL^-1 of 5p against RSR resulted in 65.4%,Carbendazim at the same concentration?84.1%?;Treatment with 250 ?g·mL^-1 of 5p and Carbendazim against FHB resulted in 74.6%and 98.1%,respectively.Systemic translation of 5p in wheat show good upward transportation,weak downward transportation and no trans-leaf effect.Carbohydrazide derivaties show wide ranges of biological activities,such as anti-pathogenic fungi,antifungal,anti-bacterial,anti-inflammatory anti-glycosidase and insecticidal.In part two,we use carbohydrazide groups replace phenylhydrazone groups link to the 1,2,3-triazole scaffold to give 20 compounds?6a-6t?.1H-NMR spectroscopy,MS were applied to confirm their molecule structures.Antifungal activity against plant-pathogenic fungi?R.solani,S.sclerotiorum,F.graminearum and M.grisea?was performed.The result indicated that these compounds were effective against all tested fungi,Compound 6g exhibited significant activity,with the EC50 values of 0.17,0.62,0.37,2.38?g·mL^-1;another compound 6m result in 0.096,0.44,0.56,0.44 ?g·mL^-1.Both of them were as good as the drug control Carbendazim,especially their antifungal activity against R.solani which EC50 value was 1.33 ?g·mL^-1.The in vivo protective effect of 6g against RSR resulted in 52.9%at a concentration of 500 ?g·mL^-1,while Carbendazim was 68.1%?The in vivo therapy activity of 6g against FHB resulted in 47.4%at a concentration of 500?g·mL^-1,while Carbendazim was 61.7%?...