RESUMEN
As part of our ongoing investigation of natural bioactive substances from the genus Thermopsis of the tribe Fabaceae for agricultural protection, the chemical constituents of the herb Thermopsis lupinoides were systematically investigated, which led to the isolation of 39 quinolizidine alkaloids (QAs) (1-39), including 14 new QAs (1-14) and 14 isoflavones (40-53). Their structures were elucidated through comprehensive spectroscopic data analysis (IR, UV, NMR, HRESIMS), ECD calculations, and X-ray crystallography. The antitomato spotted wilt virus (TSWV) and antifungal (against Botrytis cinerea, Gibberella zeae, Phytophythora capsica, and Alternaria alternata) and insecticidal (against Aphis fabae and Tetranychus urticae) activities of the isolated compounds were screened using the lesion counting method, mycelial inhibition assay, and spray method, respectively. The bioassay results showed that 34 exhibited excellent protective activity against TSWV, with an EC50 value of 36.04 µg/mL, which was better than that of the positive control, ningnanmycin (86.03 µg/mL). The preliminary mechanistic exploration illustrated that 34 induced systemic acquired resistance in the host plant by acting on the salicylic acid signaling pathway. Moreover, 1 showed significant antifungal activity against B. cinerea (EC50 value of 20.83 µg/mL), while 2 exhibited good insecticidal activity against A. fabae (LC50 value of 24.97 µg/mL). This research is promising for the invention of novel pesticides from QAs with high efficiency and satisfactory ecological compatibility.
Asunto(s)
Fabaceae , Fungicidas Industriales , Insecticidas , Antifúngicos/farmacología , Antifúngicos/química , Fungicidas Industriales/farmacología , Fungicidas Industriales/química , Alcaloides de Quinolizidina , Insecticidas/farmacología , Insecticidas/química , Antivirales/farmacología , Relación Estructura-ActividadRESUMEN
As a continuation of our research on the development of pesticide active quinolizidine alkaloids (QAs) from the family Fabaceae, the chemical constituents of the root of Sophora tonkinensis Gagnep. were systematically investigated. Seventeen new matrine-type alkaloids (1-17), including one new naturally occurring compound (17), along with 20 known ones were isolated from the EtOH extract of S. tonkinensis. Notably, compound 5 possessed an unprecedented 6/6/5/4/6/6 hexacyclic system. Their structures were confirmed via comprehensive spectroscopic data analysis (IR, UV, NMR, HRESIMS), ECD calculation, and X-ray crystallography. Biological tests indicated that compounds 1, 4, 10, 12, 13, and 30 displayed significant anti-tomato spotted wilt virus (TSWV) activities compared with the positive control ningnanmycin. Moreover, compound 12 strongly inhibited the expression of the TSWV N, NSs, and NSm genes and TSWV NSs protein in plant host. Furthermore, compounds 4, 10, 12, 20, and 22 exhibited moderate insecticidal activities against TSWV thrip vector (Frankliniella occidentalis).
Asunto(s)
Sophora , Tospovirus , Matrinas/química , Matrinas/farmacología , Tospovirus/efectos de los fármacos , Antivirales/química , Antivirales/farmacología , Espectrofotometría , Cristalografía por Rayos X , Activación Viral/efectos de los fármacos , Animales , Insecticidas/química , Insecticidas/farmacología , Proteínas no Estructurales Virales/genética , Modelos Moleculares , Estructura Molecular , Raíces de PlantasRESUMEN
As part of our ongoing investigation of pesticide active quinolizidine alkaloids (QAs) from the family Fabaceae, the chemical constituents of the seeds of Thermopsis lanceolata R. Br. were systematically investigated. Bioassay-guided fractionation and purification of the crude extract led to the isolation of seventeen new QAs (1-17), including three new naturally occurring compounds (15-17), along with 15 known compounds (18-32). Their structures were elucidated by comprehensive spectroscopic data analysis (IR, UV, NMR, and HRESIMS) and quantum chemistry calculations (13C NMR and ECD). The antitomato spotted wilt virus activities and insecticidal activities against Aphis fabae, Nilaparvata lugens (Stal), and Tetranychus urticae of compounds 1-32 were screened using the lesion counting method, spray method, and rice-stem dipping method, respectively. Biological tests indicated that compounds 6, 9, 10, and 18 displayed significant anti-TSWV activities compared with the positive control ningnanmycin. Compounds 3, 4, and 5 showed better insecticidal activities against A. fabae with LC50 values of 10.07, 12.07, and 6.56 mg/L, respectively. Moreover, compounds 5, 18, and 24 exhibited moderate insecticidal activities against N. lugens (Stal) with LC50 values of 37.91, 53.44, and 31.21 mg/L, respectively. Furthermore, compounds 9 and 10 exhibited moderate insecticidal activities against T. urticae.
Asunto(s)
Alcaloides , Áfidos , Fabaceae , Insecticidas , Quinolizidinas , Alcaloides/análisis , Alcaloides/farmacología , Animales , Insecticidas/química , Quinolizidinas/farmacología , Semillas/químicaRESUMEN
Currently, there is insufficient viricide to effectively control tomato spotted wilt virus (TSWV). To address this pending issue, a series of thienopyrimidine-containing dithioacetal derivatives were prepared and tested for their anti-TSWV activities. A subsequent three-dimensional quantitative structure-activity relationship was constructed to indicate the development of optimal compound 35. The obtained compound 35 had excellent anti-TSWV curative, protective, and inactivating activities (63.0, 56.6, and 74.1%, respectively), and the EC50 values of protective and inactivating activities of compound 35 were 252.8 and 113.5 mg/L, respectively, better than those of ningnanmycin (284.8 and 144.7 mg/L) and xiangcaoliusuobingmi (624.9 and 300.0 mg/L). In addition, the anti-TSWV activity of compound 35 was associated with defense-related enzyme activities, enhanced photosynthesis, and reduced stress response, thereby enhancing disease resistance.
Asunto(s)
Tospovirus , Resistencia a la Enfermedad , Humanos , Enfermedades de las Plantas , PirimidinasRESUMEN
A number of chromone derivatives containing sulfonamide structure were designed and synthesized. Firstly, the target compounds were evaluated for anti-TSWV activities in vivo by the half-leaf method. We found that most of the compounds had good anti-TSWV activities. Among them, compound 12B had excellent anti-TSWV inactivating activity with an EC50 of 80.5 µg/mL, which was significantly better than xiangcaoliusuobingmi (765.7 µg/mL). Secondly, TSWV nucleocapsid protein (N) was expressed and purified, and the affinity between the compounds and TSWV N was tested by microscale thermophoresis (MST). Compound 12B had a good affinity for TSWV N with a Kd value of 5.02 µM, which was superior to xiangcaoliusuobingmi (29.83 µM). Finally, in order to study the mode of interaction between the compound 12B and TSWV N, we carried out molecular docking. The results indicated that compound 12B might inactivate the virus by destroying the TSWV N oligomer structure. These results lay a solid foundation for the further discovery of chromone derivatives containing sulfonamide structure with high anti-TSWV activities.
Asunto(s)
Antivirales/farmacología , Cromonas/farmacología , Descubrimiento de Drogas , Sulfonamidas/farmacología , Tospovirus/efectos de los fármacos , Antivirales/síntesis química , Antivirales/química , Cromonas/síntesis química , Cromonas/química , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Relación Estructura-Actividad , Sulfonamidas/químicaRESUMEN
A series of unreported novel dithioacetal derivatives containing a 4(3H)-quinazolinone pyrimidine ring were synthesized, and their antiviral activities were evaluated against tomato spotted wilt virus (TSWV). A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was established, and compound D32 was designed and synthesized according to the analysis results of the CoMFA and CoMSIA models. The bioassay results showed that compound D32 exhibited excellent inactivation activity against TSWV, with EC50 values of 144 µg/mL, which was better than those of ningnanmycin (149 µg/mL) and the lead compound xiangcaoliusuobingmi (525 µg/mL). The binding ability of compound D32 to TSWV CP was tested by microscale thermophoresis (MST), and the binding constant value was 4.4 µM, which was better than those of ningnanmycin (6.2 µM) and xiangcaoliusuobingmi (59.1 µM). Therefore, this study indicates that novel dithioacetal derivatives containing a 4(3H)-quinazolinone pyrimidine ring may be applied as new antiviral agents.