Synthesis,Biological Activity,Structure-Activity Relationship And Photodegradation Studies Of 3-Amino-5-Carboxyl-1,2,4-Triazole Schiff Base Derivatives

Drug molecules with 1,2,4-triazole structure are widely used in the field of pesticides due to their low toxicity,high efficiency,broad spectrum and unique mechanism of action.Their derivatives can effectively prevent crops from being infected by plant diseases,so as to improve the yield and quality of crops,but with its long-term use,the sensitivity of microorganisms to drugs is enhanced.Based on this,the intermediate substituted benzaldehyde used pesticides,medicines and plant growth regulators was introduced into the1,2,4-triazole ring by using the principle of structural splicing to develop novel bactericidal drugs with high efficiency and strong drug resistance in this paper.First,14 compounds were synthesized by 3-amino-5-carboxyl-1,2,4-triazole and substituted benzaldehyde.Their structures were characterized by melting point test,elemental analysis and spectroscopic techniques(IR,¹H NMR,¹³C NMR),and bioactivity against Fusarium graminearum,Maize rough dwarf bacteria and Glomerella cingulate were also analyzed.According the EC₅₀value,the inhibitory effects of 8 and 6 compounds against Fusarium graminearum and Maize rough dwarf bacteria were superior to that of the standard drug fluconazole,respectively,while only compound AS-14 was more active than fluconazole against Glomerella cingulate.Additionally,the inhibitory activities of 14 compounds compounded with pyrimethanil（5mass ratios）against Fusarium graminearum found that except for compounds AS-1,AS-3 and AS-10,the others had one or several systems of synergistic effect,in which,AS-7 and pyrimethanil at a mass ratio of 4:1 had significant synergistic effect.The structural parameters,molecular stable configurations,molecular frontier orbitals and surface electrostatic potentials of 14 compounds were obtained by DFT/B3LYP/6-31G and DFT/B3LYP/6-311G methods.The orbitals energy difference affects the activity of the three fungi,and the surface electrostatic potential predicts the electrophilic and nucleophilic sites of the compounds.Based on the principal component analysis of parameters calculated by Gaussian 09 and Hyperchem software,20 structural parameters affecting the activity were screened.Then,these parameters were correlated with the inhibitory activity(Log(1/EC₅₀))of the three pathogenic bacteria to construct 2D-QSAR equation.The results exhibited the charge of the nitrogen atom on the triazole(Q_N2)and molecular stability energy（HF）,the dipole moment（Pe）and relative molecular mass（M）,the charge of the imino N atom(Q_N5)and the hydration energy of the molecule（HE）were the most important factors affecting the activity of Fusarium graminearum,Maize rough dwarf bacteria and Glomerella cingulate,respectively.The synthesized compounds were respectively docked with the receptor protein 5E9H by molecular docking software.The results found that when the same position on the benzene ring was substituted,the smaller the binding energy,the stronger the inhibitory ability against Fusarium graminearum.Moreover,the toxicological and pharmacokinetic properties of 14compounds showed that except for AS-1,AS-9,AS-10 and AS-14,the other compounds displayed no tumorigenic,mutagenic,reproductive and irritant.The compounds（except for AS-1 and AS-12）had better human plasma protein binding capacity and higher intestinal absorption capacity.Finally,the photodegradation behavior of the target compounds conformed to the first-order kinetic equation,and it was easier to be degraded when the benzene ring connected with the electron-withdrawing group.