Design, Synthesis And Biological Activity Of Sulfonamide-containing Imidazo[1,2-a]pyridine Mesoionic Compound

In this paper,triflumezopyrim was used as the lead compound,and the sulfonamide structure was introduced through the principle of active splicing,then,we successfully designed and synthesized 33 mesoionic compounds bearing a sulfonamide moiety.Taking tomato spotted wilt virus（TSWV）and potato virus Y（PVY）as research objects,the antiviral activity of the target compounds were tested by the half leaf spot method.Compound A33 was derived based on the 3D-QSAR model that was constructed by the EC₅₀values of the synthetic compounds’protective activities.Antiviral activity tests suggested that A33 exhibited excellent anti-PVY activity.Significantly,defensive enzyme activities and proteomics results indicated that compound A33 could enhance the defense response by activating the activity of defense enzymes,inducing glycolysis/gluconeogenesis pathway of tobacco to resist the infection of virus.The work of this paper is summarized as follows:1.Triflumezopyrim was used as the lead compound,and the sulfonamide moiety was introduced through the principle of active splicing,then,we have successfully designed and synthesized 33 mesoionic compounds bearing a sulfonamide moiety.The structures of target compounds A1-A33 were determined by ¹H NMR,¹³C NMR,and HRMS.2.The anti-PVY activities of compounds A1-A32 were preliminarily screened by the half-leaf method using Chenopodium amaranticolor plants at a concentration of500 mg/L.The experimental results showed that the compounds A13（49.9%,61.0%,83.0%）,A31（53.9%,61.3%,81.5%）were better than NNM in the curative,protective and inactivating activities（47.2%,50.1%,81.4%）.The protection EC₅₀value of most of the target compounds against PVY was better than that of NNM（432.2 mg/L）.The EC₅₀values of compounds A4,A5,A13,A15,and A31 were199.2,161.3,205.4,218.8,and 149.3 mg/L,which was significantly better than NNM.3.The anti-TSWV activities of compounds A1-A33 were preliminarily screened by the half-leaf method using Nicotiana glutinosa plants at a concentration of 500mg/L.The experimental results showed that anti-TSWV activity of most of the target compounds was average.And their curative,protective,and inactivating activities did not exceed that of ningnamycin（NNM,59.6%,65.6%,67.2%）,but some compounds such as A10,A12,A13,A14,A15,A21,A22,A24,A29,A32 were better than Ribavirin in the curative,protective and inactivating activities（41.2%,43.8%,48.7%）.4.In order to analyze the structure-activity relationship of the target compounds,we build a 3D-QSAR model based on EC₅₀of the anti-PVY protective activities of the target compounds.The q²,r²of the Co MFA model were 0.618,0.929.The q²,r²of the Co MSIA model were 0.687,0.937,respectively,it proved that these models had good stability and prediction ability.Equipotential analysis showed that the activity of the imidazo[1,2-a]pyridine mesoionic compounds containing a sulfonamide moiety was mainly affected by the steric and electrostatic fields.Based on this models,compound A33 was further designed and synthesized.The experimental results showed that the EC₅₀value of the protective activity of compound A33 was 117.9 mg/L,which was significantly better than that of NNM.5.Based on the protective activity of compound A33 against PVY,its defense enzyme activity test and proteomic study were carried out.The results showed that compound A33 could enhance the defense response by activating the activity of defense enzymes,inducing glycolysis/gluconeogenesis pathway of tobacco to resist the infection of PVY.