Screening And Preliminary Structure-activity Relationship Study Of Inhibitor Of Type Ⅲ Secretion In Xanthomonas Oryzae Pv.Oryzae

Bacterial blight(bacterial disease)and blight(fungal disease)are important factors of biotic stress limiting rice production in the world.Bacterial blight of rice is one of the rice diseases caused by Xanthomonas oryzae pv.oryzae(Ishiyama),Xoo.Plants were infested at any stage of rice growth.At present,chemical control is the main way to control bacterial blight in rice.However,traditional fungicides have poor control effects and even lead to enhanced resistance to pathogens.Therefore,the search for antimicrobial agents with novel mechanisms has important market prospects and application value.The bacterial type Ⅲ secretion system(T3SS)is an important virulence factor of Xoo.It secretes effector proteins into the host during pathogen infection.Therefore,this system can provide novel targets for the design of drug molecules.Previous studies have shown that TS006-based polyphenolic compounds as novel T3SS inhibitors have a good preventive effect against rice bacterial blight.This thesis is based on the screening model of Xoo T3SS inhibitor established by the research group,TS006 was used as a positive control,detection of inhibitory activity of 216compounds synthesized in the early stage on hpal gene promoter by high-throughput screening(HTS);Detecting the Effect of high active compounds on the growth of Xoo;The effect of active compounds on the HR reaction of Xoo on tobacco was tested;Detecting the effect of T3SS inhibitors on Xoo pathogenicity in rice seedlings and adult plants;And two types of bacterial blight blight T3SS inhibitors with novel structural framework were identified,namelyβ-nitrophenene compounds(YM-2,YM-10)andβ-nitrophenylallylpropionic acid compounds(ZGX-7,XY-254).The results showed that the inhibitory rate of 100 μ mol/L β-nitrophenylalanine XY-254 on hpa1 promoter was 97%,while the inhibitory rate of 200μmol/L positive control TS006 on hpa1 promoter was only 77%.The inhibitory rate of the compound on the hpa1 promoter increased with increasing concentrations,showing a significant concentration dependence.In the rich medium(M210)and hrp induction medium(XOM2),The compound did not show significant inhibition on the adaptation period,growth period,stationary phase,and decline phase of Xoo,indicating that each growth stage of the bacteria was not affected.At the same time,compound XY-254 was able to inhibit the HR reaction of Xoo on tobacco;It also could well inhibit the pathogenicity of Xoo on rice seedlings and adult plants,indicating it can be a potential T3SS inhibitor.In addition,the paper is based on the above results,using the compound XY-254 as a lead compound,a series of structural derivatives 2a-7d were designed and synthesized using the principle of constrained confinement,the principle of bio-isosteric displacement,and the principle of combination.Chemical structures confirmed by ~1HNMR,but its biological activity needs further study.In this dissertation,216 compounds were screened by four experimental methods,four small-molecule compounds with inhibitory effect on rice bacterial blight were screened.Then optimize the design and synthesis of new compounds for the most active compound XY-254.