| Biotin,one of the B vitamins,is a water-soluble vitamin.Biotin is a crucial coenzyme in biocarboxylate transcarboxylation,which plays an important role in the metabolism of sugars,biosynthesis of fatty acids and amino acid metabolism in microorganisms,plants and animals.Plants,microorganisms can synthesize their own biotin,but the enzymes involved in biotin synthesis are not present in higher animals,so the synthetic inhibitors based on the enzymes involved in the biotin synthesis process can be maximized to reduce the toxicity of non-target organisms.Dethiobiotin synthetase is the most deeply studied biotin synthase.In this study,two series of compounds were designed and synthesized based on dethiobiotin synthetase.The main results were as follows:1.With 5-bromo-2,3-diaminopyridine as the material,the intermediate compound 6-bromo-1-isopropenyl-1H-imidazo [4,5-b] pyridin-2-one was prepared by cyclization of ethyl acetoacetate,and then 17 new 6-bromo-1-isopropenyl-1H-imidazo [4,5-b] pyridin-2-one amide derivatives were obtained by N-acylation reaction.2-amino 4,6-dimethoxypyrimidine was synthesized from 2-chloro-4,6-dimethoxypyrimidine via ubstitution reaction,fllowed by Nacylation and etherification reaction to obtain 26 pyrimidin-2-amine derivatives.The structure of all compounds was identified by 1H-NMR,13C-NMR,and ESI-MS,respectively,and its physical data were tested accurately.2.Using filter paper method,all the compounds were tested on antimicrobial activity in vitro againsit the six pathogenetic bacteria : Erwinia carotovora,Bacillus cereus,Escherichia coli,Staphyloccocus aureus,Xanthomonas oryzae pv.Oryzae,Pseudomonas syringae pv.actinidiae.In general,the inhibitory activity of the target compounds against the six tested bacteria was not significant.Only compounds B-03,B-05,B-13,MD-06,MD-17 and MD-21 were resistant to Bacillus cereus activity slightly better.3.The inhibitory activity of the obtained compounds on the mycelial growth of the tested fungi was evaluated by the growth rate method,and the inhibitory concentration(IC50)of the compounds with high activity was determined.The activity test results showed that 6-bromo-1-isopropenyl-1H-imidazo [4,5-b] pyridin-2-one compounds B-01(acetyl derivative),B-03(phenylacetyl derivative)B-04(propionyl derivatives),B-05(cyclopropanyl derivatives),B-06(butyryl derivatives)and B-13(o-chlorobenzoyl derivatives)have a significant inhibitory effect on the mycelial growth of some tested fungi,especially in the compounds the antibacterial activity of B-06 is most prominent against Fusarium graminearum and Botrytis cinerea,and the IC50 values were 8.23,4.01 g/mL.The inhibitory activity of 2-amino-4,6-dimethoxypyrimidine derivatives was only obvious for the mycelial growth of Botrytis cinerea and Sclerotinia sclerotiorum,among which the activity of MD-09(cyclopropionyl derivatives)MD-16(heptanoyl derivatives),MD-20(m-methylbenzoyl derivatives),MD-22(o-chlorobenzoyl derivatives)is particularly prominent.While MD-09 on Sclerotinia sclerotiorum had a most prominent activity,and the IC50 value is 4.92?g / mL.4.Using inhibition of spore germination method,all the compounds were tested on antifungal activity in vitro against Curvularia lunata.Toxicity test was carried out for the compounds whose spore germination inhibition was high.The activity of compound B-04 and compound B-06 was better,and the IC50 was 17.30 and 14.67?g / mL,respectively.5.The inhibitory effect of the compound against B.Cinerea was verified by the experiment on fresh tomato fruit.The results showed that tested compounds B-01,B-06,MD-09,MD-20 and MD-26 exhibited a good inhibitory activity of fungi,and the inhibitory rate was more than 50% at the concentration of 200?g/mL,which provided a basis for development of new pesticides.6.Comparing the dethiobiotin addition test and molecular docking score,the results showed that the antifungal target of 2-amino-4,6-dimethoxypyrimidine derivatives provided preliminary theoretical basis for dethiobiotin synthetase. |
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