Synthesis And Biological Activity Of Pentadienone And Chalcone Derivatives Containing Thiophene Sulfonate

In this paper,pentadienone and chalcone are used as lead compounds.Using the principle of active splicing,thiophene sulfonate is introduced into the structure of pentadienone and chalcone to synthesize 22 pentadienone containing thiophene sulfonate Derivatives ?1-?22 and 22 chalcone derivatives ?1-?22 containing thiophene sulfonate,and tested them for antibacterial?Xac?Xoo and Rs?and antiviral?TMV?activity.All compounds were characterized by ¹H NMR?¹³C NMR and HRMS.The main findings of this paper are as follows:At mass concentrations of 100 and 50?g/mL,the fungicides thiodiazole copper?TC?and bismerthiazol?BT?were selected as control agents to test the synthesized target compounds against Xanthomonas axonopodis pv.Citri?Xac?,Xanthomonas oryzae pv oryzae?Xoo?and Ralstonia solanacearum?Rs?in vitro.Inhibitory activity.The test results show that all compounds have certain inhibitory activities against the above three strains.Among them,the inhibitory rates of compounds ?11??12??18and ?12 on Xac were 99.1?80.1?98.3 and 95.2%,respectively,which were superior to those of the control agents TC?57.2%?and BT?65.3%?.The inhibitory rates of compounds ?11??13?I21??6??12 and ?21 on Xoo were 84.3?96.3?88.3?88.1?82.3 and 83.3%,respectively,which were better than the control agents TC?50.2%?and BT?64.9%?.The inhibitory rates of compounds ?15??13??15and ?16 on Rs were 89.3?91.4?92.4 and 85.2%,respectively,which were superior to those of the control agents TC?45.2%?and BT?53.7%?.Further research showed that the EC₅₀values of compounds ?11,?18,and ?12 against Xac were 11.0?18.2and 11.4?g/mL,respectively,which were better than those of the control agents TC?94.7?g/mL?and BT?51.6?g/mL?.).The EC₅₀values of compounds ?11??13 and ?6 against Xoo were 25.0?22.6 and 19.1?g/mL,respectively,which were better than those of the control agents TC?97.8?g/mL?and BT?71.7?g/mL?.The EC₅₀values of compounds ?13 and ?15 against Rs were 11.6 and 25.0?g/mL,respectively,which were better than those of the control agents TC?78.8?g/mL?and BT?98.6?g/mL?.The possible antibacterial mechanism of the target compounds?11and?12 on citrus canker was explored by scanning electron microscope imaging.We tested all compounds against tobacco mosaic virus?TMV?at a concentration of500?g/mL.The results showed that the inhibitory activities of compounds ?1??4??12??16??1??5??8??12??13 and ?15 on TMV were 70.7?73.1?74.0?70.5?72.5?84.2?73.5?81.8?72.6 and 75.3%,better than ningnanmycin?53.3%?;In terms of protective activity,the inhibitory activities of compounds ?7??8??9??10?I20??1??5??8 and ?12 on TMV were 76.4?70.2?70.1?72.0?72.5?70.0?75.2?71.8?and 72.8%,respectively,which are better than ningnanmycin?62.6%?;In terms of passivation activity,the inhibitory activities of compounds ?1??11??1??5 and ?8 on TMV are 83.1?86.6?80.1?87.3 and 81.1%were better than ningnanmycin?78.3%?.In order to further study the anti-TMV activity of compounds,we tested the EC₅₀of some compounds with good preliminary screening activity.Among them,the EC₅₀values of anti-TMV therapeutic activity of compounds ?1?I4??12??16??1??5??8 and ?12 were 274.9?262.3?237.7?274.8?256.1?178.0?279.2 and 258.5?g/mL,which were superior to commercial drugs EC₅₀value of ningnanmycin?403.7?g/mL?.The EC₅₀values of compounds I7?I8?I9??10?I20??5??8?and ?12 against TMV protection were 233.9?286.3?288.9?267.9?261.8?269.0?287.4 and 282.6?g/mL,which were superior to commercial drugs EC₅₀value of ningnanmycin?317.0?g/mL?.The EC₅₀values of compounds ?1??11??1??5??10 and ?15 against TMV passivation were 92.8?85.3?80.6?44.3?62.2 and 79.3?g/mL,which were better than the EC₅₀values of the control drug ningnanmycin?120.6?g/mL?.Microscale thermophoresis?MST?experiments show that the K_dvalues of compounds ?5 and ?8 and tobacco mosaic virus-coat protein?TMV-CP?are 0.27 and 0.19?mol/L,respectively,which is superior to the control drug ningnanmycin,indicating that they have a strong interaction with TMV-CP.Molecular docking experiments showed that the molecular docking of compounds ?5 and ?8 with TMV-CP found that small molecules penetrate deep into the active pockets formed by amino acid residues ARG 46,ARG90,THR42,THR37 and GLN34,indicating that ?5 and ?8 and TMV-CP There is a strong binding force between them.