Synthesis And Biological Activity Of Triazine-containing Pentadienone And Chalcone Derivatives

As important curcumin analogs,penta-1,4-diene-3-ones have been widely researched and used in medicinal and agrochemical development because of their extensive biological properties,including antibiotic,antiviral,insecticidal,anticancer,anti-oxidative and anti-inflammatory activities,and it has become one of the hot spots in pharmaceutical innovation.Notably,their visible antiviral and antibacterial activities against plant have been reported well in recently.At the same time,chalcone and derivatives,a natural organic compound,are widely used in agriculture because of their well biological activities such as antibiotic,antiviral and insecticidal activities.Meanwhile,1,2,4-triazine and their derivatives have played vital roles in agrochemical development due to their outstanding characteristics,including high activity,unique action mechanism and broad spectrum.Considering these above findings,series of penta-1,4-diene-3-one derivatives bearing 1,2,4-triazine or chalcone derivatives bearing 1,2,4-triazine,which confirmed by ¹H NMR,¹³C NMR and HRMS were designed and synthesized through introducing 1,2,4-triazine groups to the penta-1,4-diene-3-one or chalcone.The paper’s main work and findings are summerized bellow:1.Twenty-three chalcone derivatives bearing 1,2,4-triazine moiety were designed and synthesized in the present work.Using the commercial agent ningnanmycin as the control under the same conditions,their antiviral activities against tobacco mosaic virus（TMV）were tested at concentration of 500μg/mL based on the half leaf blight spot method.In terms of their curative activities,the compounds T12（62.7%）,T15（61.4%）,T21（65.6%）and T23（60.6%）,which were better than ningnanmycin（45.7%）.In terms of their protective activities,the inhibitory rates of compounds T2,T7,T15 and T21 are 58.7%,55.5%,55.9%and 62.7%respectively,which were better than that of ningnanmycin（53.4%）.Moreover,the compounds T11 effectively inactivated TMV,with the inhibitory rates of 86.8%,which was better than ningnanmycin（77.3%）.Further biological assay indicates that the EC₅₀values of compounds T7 and T11 in terms of their curative activities were 17.5 and 21.8μg/mL,which were better than that of ningnanmycin（81.4μg/mL）.Compounds T12and T21 exhibited the best protective activity against TMV,with EC₅₀values of 79.4and 52.4μg/mL,respectively,which were better than that of ningnanmycin（82.3μg/mL）.Notably,compound T11 was found to exhibit significant inactivation activity（2.5μg/mL）,which was better than that of ningnanmycin（13.5μg/mL）.Using the commercial agents thiodiazole-copper and bismerthiazol as the control under the same conditions,the antibacterial activities of some title compounds against Xanthomonas axonopodis pv.citri（Xac）and Ralstonia solanacearum（R.s）and Xanthomonas oryzae pv.Oryzae（Xoo）at concentration of 100 and 50μg/mL were evaluated based on the turbidimeter test.Bioassays indicated that some compounds exhibited good antibacterial activities.At a concentration of 100μg/mL,the target compounds have a certain inhibition rate on Xoo.Moreover,compounds T1,T14,T18 and T23presented excellent antibacterial activities against R.s at 100μg/mL,with the inhibition rates of 93.7%,99.9%,96.7%and 94.2%,respectively,which were higher as compared to bismerthiazol（52.1%）and thiadiazole-copper（80.2%）.In addition,compounds T5,T10,T13 and T14 at 100μg/mL,exhibited better antibacterial activities against Xac than bismerthiazol（70.5%）and thiodiazole-copper（75.9%）,with the values of 93.1%,96.8%,88.0%and 87.7%,respectively.Further biological assay indicates that the EC₅₀values of compounds T1 for R.s reached 0.1μg/mL.At the same time,compounds T1 exhibited satisfactory in vitro antibacterial activities against Xac,with the EC₅₀values of 53.6μg/mL,which was higher than that of bismerthiazol（153.7μg/mL）and thiodiazole-copper（77.8μg/mL）.furthermore,compound T7 was found to exhibit higher antibacterial activity against Xoo（76.7μg/mL）,which was better than that of bismerthiazol（94.5μg/mL）.A plausible antiviral mechanisms of this kind of compounds against tobacco mosaic virus or against tobacco bacterial wilt（R.s）were proposed and confirmed by the microscale thermophoresis,molecular docking and scanning electron microscopy.2.Eighteen penta-1,4-diene-3-one derivatives bearing 1,2,4-triazine moiety were designed and synthesized in the present work.Using the commercial agent ningnamycin as the control under the same conditions,their antiviral activities against TMV were tested at concentration of 500μg/mL based on the half leaf blight spot method.In terms of their curative activities,the compounds X6（53.8%）、X11（66.3%）、X12（59.9%）and X13（48.8%）,which were better than ningnanmycin（45.7%）.In terms of their protective activities,the inhibitory rates of compounds X2 and X8are 54.5%and 61.4%,respectively,which were better than that of ningnanmycin（53.4%）.Moreover,the compounds X1 effectively inactivated TMV,with the inhibitory rates of 66.2%,which was similar to ningnanmycin（77.3%）.Further biological assay indicates that the EC₅₀values of compounds X11 and T11 in terms of their curative activities were 11.5 and 12.1μg/mL,which were better than that of ningnanmycin（81.4μg/mL）.Compound X4 exhibited the best protective activity against TMV,with EC₅₀values of 37.6μg/mL,which was better than that of ningnanmycin（82.3μg/mL）.Notably,compound X1 was found to exhibit significant inactivation activity（12.5μg/mL）,which was better than that of ningnanmycin（13.5μg/mL）.Using the commercial agents thiodiazole-copper and bismerthiazol as the control under the same conditions,the antibacterial activities of some title compounds against Xanthomonas axonopodis pv.citri（Xac）and Ralstonia solanacearum（R.s）and Xanthomonas oryzae pv.Oryzae（Xoo）at concentration of 100 and 50μg/mL were evaluated based on the turbidimeter test.The results of biological activity test showed that the compounds had certain inhibitory activity against Xoo and R.s at a concentration of 100μg/mL.Moreover,compounds X11 and X12 at 100μg/mL,exhibited better antibacterial activities against Xac than bismerthiazol（70.5%）and thiodiazole-copper（75.9%）,with the values of 91.8%and 95.4%.Further biological assay indicates that the EC₅₀values of compounds T1 exhibited satisfactory in vitro antibacterial activities against R.s,with the EC₅₀values of 0.43μg/mL,which was higher than that of bismerthiazol（49.5μg/mL）and thiodiazole-copper（36.1μg/mL）.