| In this study,40 indoles containing 4,5-dihydro-1H-pyrazolines were designed and synthesized employing indole derivatives as lead compounds,and the structure of4,5-dihydro-1H-pyrazolines with broad-spectrum activity was introduced using the structural splicing approach.Using the half-leaf method and Potato virus Y(PVY)as the exploratory focus,the anti-PVY activity of each agrochemical was assessed.On the basis of the inhibition medium concentration(EC50)of the anti-PVY protective activity as a function of the target compound and the structural characteristics as independent variables,a three-dimensional quantitative conformational relationship analysis(3D-QSAR)was assembled to simulate the higher anti-PVY activity of the target compound D40.Lastly,a preliminary explanation of the anti-PVY mechanism of action of the target chemical D40 was conducted by assessing tobacco tissue defense enzymes and doing proteome analyses.Below is a description of the main body of this thesis:1.Using indole derivatives with antiviral activity as lead compounds and incorporating 4,5-dihydro-1H-pyrazoline structures with broad-spectrum biological activity,40 indoles containing 4,5-dihydro-1H-pyrazoline were designed and synthesized.1H NMR,13 C NMR,19 F NMR,and HRMS were employed to determine the structures of compounds D1-D40.2.At a concentration of 500 μg/m L,all compounds were evaluated for anti-PVY efficacy using Chenopodium amaranticolor plants as PVY blight hosts.The activity assessments reveal that the majority of the target compounds illustrated powerful curative,protective and inactivating activities,D8(52.5%,58.7%,and 83.8%),D16(60.0%,52.1%,and 82.4%),D20(63.1%,52.6%,and 82.8%),D34(55.3%,60.4%,and 82.8%),and D36(56.5%,56.8%,and 84.5%),they were superior than ningnanmycin(47.2%,50.1%,and 81.4%,respectively);D4(220 μg/m L),D8(224μg/m L),D25(204 μg/m L),D30(229 μg/m L),and D34(208 μg/m L)affirmed considerably vastly higher protective EC50 activity than ningnanmycin(419 μg/m L).3.On the basis of the EC50 values for the anti-PVY protective activity of this series of pharmaceuticals,cross validation coefficient(q2),a non-cross-validated calculation of the correlation coefficient(r2)and standard deviation was used to acquire a 3DQSAR model.q2 and r2 of the Co MFA model were 0.736 and 0.968,respectively;q2and r2 of the Co MSIA model were 0.609 and 0.913,respectively;q2 > 0.500 and r2 >0.900 confirmed that the model was able to accurately predict the structures of the target compounds.The residual analysis of the experimentally determined p EC50 and the anticipated p EC50 values,as well as the plotting of the regression equations,emphasizing that both of the intellectuals’ models are capable of meticulous prophecy.The examination of 3D isopotential plots revealed that both the spatial steric field and the electrostatic field had an influence on the antiviral activity of the target compounds,with the spatial steric field contributing 0.513 to the activity and the electrostatic field contributing 0.487 to the activity.Based on this model,compound D40 was further designed and synthesized,and the test results showed that D40(50.2%,50.7%,82.1%,and 419 μg/m L)was significantly better than ningnanmycin(64.9%,60.8%,84.9%,and 202 μg/m L)in terms of curative,protective,inactivating activities and protective EC50 value.4.Proteome and defensive enzyme activity tests were done based on the fact that the target chemical D40 protected very well against PVY.The experimental results demonstrated that D40 could optimize the activity of tobacco’s defense enzymes.In the meantime,proteomic studies demonstrated that D40 triggered an immunemediated resistance response to boost the plant’s resistance to the virus via the controlled photosynthetic carbon fixation pathway. |
PDF Full Text Request