| Herbicides,as a vital means of agricultural production,have played an important role in ensuring the stable production and income of crops.With the long-term and widespread use of herbicides,many problems such as residual phytotoxicity and weed resistance have appeared.Therefore,the development of herbicides with new targets and novel structures has far-reaching significance for the benefit of the country and the people in the development of agricultural production.In this study,transketolase was used as the target protein of the herbicide,combined with the herbicide lead structure pyrimidine pyrazole amine compound 4u obtained earlier,and through molecular design,molecular docking and activity screening techniques,in order to obtain compounds with excellent herbicidal activity.The specific research content is as follows:In this study,pyrazolamine molecules were used as lead compounds,and a series of compound molecules were designed through methods such as skeleton transition and active group splicing.Through molecular docking technology,the designed compound molecules were modeled with the homology model.The three-dimensional structure model of mustard transketolase AtTKLl was docked in order to screen for compounds with higher biological activity.Through the analysis of the docking results,33 target compounds with higher binding energy were obtained,which interacted with the key catalytic amino acids His103 and His340 in the transketolase activity cavity through van der Waals forces,indicating that the target compounds may behave a higher herbicidal activity.They were synthesized preferentially,and finally 33 target compounds were obtained,the structures of which were confirmed by 1H NMR,13C NMR and HRMS,and their herbicidal activity was also obtained through experiments.In this study,single crystals of the target compound were cultured with a solvent ratio of dichloromethane:ethyl acetate of 20:1,and single crystals of representative compoundⅣ-16 were obtained.The single crystals of the representative compound IV-16 were passed through a Bruker Smart diffractometer through graphite monochromatic radiation.(MoKα(λ=0.71073 A))was diffracted,and the single crystal diffraction data of compoundⅣ-16 was collected by φ-ω scanning at 113(2)K.The single crystal structure is completely consistent with the designed structure,so it is more accurately confirmed the correct structure of the target compound in this test.The synthesized target compounds were tested in vitro and in pots by two methods:small cup method and stem and leaf spray method,in order to evaluate their herbicidal activity.Through the small cup method test,under the condition of a concentration of 200 mg/L,the growth inhibition rate of compounds Ⅳ-1,Ⅳ-4,Ⅳ-17,Ⅳ-26,Ⅳ-27 and Ⅳ-28 on B.campestris roots respectively 99.34%,100%,94.94%,94.79%,94.91%and 96.23%,of which compound Ⅳ-4 completely inhibits the growth of B.campestris roots,which is significantly better than the control compound 4u and the control drug atrazine;in addition,compounds Ⅳ-1,Ⅳ-4 and Ⅳ-27 have 96.65%,100%and 95.84%inhibition rates on the growth of B.campestris stems.Compound Ⅳ-4 can completely inhibit the growth of B.campestris stems,which is significantly better than the the control compound 4u and control agent atrazine;The inhibitory rates of compound Ⅳ-16,Ⅳ-18 and Ⅳ-19 on the roots of A.were 72.01%,70.16%and 76.63%,which were significantly better than the control compound 4u and the control agent atrazine;at the same time,the inhibitory rates of the compounds Ⅳ-1,Ⅳ-11,Ⅳ-16 and Ⅳ-27 on the stems of A.retroflexus were 74.48%,74.43%,81.27%and 74.13%,which were significantly better than the control compound 4u and the control agent atrazine;in addition,The inhibition rates of the compounds Ⅳ-6 and Ⅳ-8,Ⅳ-11 and Ⅳ-13 on D.sanguinalis were 73.25%,69.65%,78.09%and 76.21%,which were significantly better than the control agent atrazine.Measured by the stem and leaf spray test,the growth inhibition rates of compounds Ⅳ-1,Ⅳ-2,Ⅳ-4 and Ⅳ-27 on the fresh weight of B.campestris were 75.25%,70.55%,83.78%and 81.78%,respectively,which were significantly better than the control compound 4u and the control agent atrazine;compound Ⅳ-9 and Ⅳ-16 have 66.83%and 80.68%inhibition rates on the fresh weight of A.retroflexus,which were significantly better than the control compound 4u;the inhibitory rates of compound Ⅳ-27 and Ⅳ-31 on the fresh weight of D.sanguinalis were 56.75%and 59.38%,which were significantly better than the control compound 4u and the control agent atrazine;the herbicidal activity of the target compound measured by the stem and leaf spray method was slightly lower than that of the small cup method.Perhaps due to the waxy layer on the surface of the plant leaves in the pot,the relatively simple formulation processing failed to make the compound molecules reach their targets.In summary,compound Ⅳ-27 showed good herbicidal activity and is worthy of further study. |
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