Synthesis of tetrazole containing 1,2,3-thiadiazole derivatives via U-4CR and their anti-TMV activity

A series of novel tetrazole containing 1,2,3-thiadiazole derivatives were designed and synthesized via Ugi reaction. Their structures were confirmed by melting points, IR, 1H NMR, and HRMS (ESI). Preliminary bioassay indicated that most target compounds exhibited very good direct anti-TMV activity at 100 μg/mL, which was equal to or higher than that of ribavirin. Among them, compounds 4b, 4c and 4i also showed equivalent protection effect to ribavirin in vivo at 100 μg/mL.     

含喹喔啉杨梅素衍生物的合成及生物活性

利用活性拼接原理, 将喹喔啉引入到杨梅素结构中, 合成了一系列含喹喔啉基团的杨梅素新型衍生物. 采用浊度法测试了目标化合物的体外抑菌活性, 结果表明, 目标化合物对柑橘溃疡病菌(X. Citri)和水稻白叶枯病菌(X. Oryzae)均表现出较好的抑制活性. 目标化合物对柑橘溃疡病菌的抑制活性(EC₅₀)均优于对照药叶枯唑和噻菌铜(EC₅₀分别为54.85和61.13 μg/mL), 其中化合物4o抑制活性(EC₅₀=11.17 μg/mL)最优; 目标化合物对水稻白叶枯病菌的抑制活性EC₅₀均优于对照药叶枯唑和噻菌铜(EC₅₀分别为148.20和175.47 μg/mL), 其中化合物4f抑制活性(EC₅₀=34.49 μg/mL)最优. 采用半叶枯斑法测试了目标化合物的抗烟草花叶病毒(TMV)活性, 结果表明, 所有目标化合物在浓度为500 mg/L时均有一定的抑制作用.     

Synthesis and biological activities of novel dialkyl (4-trifluoromethylphenylamino)-(4-trifluoromethyl or 3-fluorophenyl) methylphosphonates

A series of novel dialkyl (4-trifluoromethylphenylamino)-(4-trifluoromethyl or 3-fluorophenyl) methylphosphonates 3 were synthesized through the reaction of 3-fluorobenzaldehyde or 4-trifluoromethylbenzaldehyde and 4-trifluoromethylaniline with dialkyl phosphite by microwave irradiation using boron trifluoride-ether catalyst and their structures were clearly verified by spectroscopic data (IR, ¹H NMR and elemental analysis). The results of bioassay showed that these title compounds possess potential anticancer activities in vitro by MTT method. At the same time, we found these title compounds exhibit moderate antiviral activity against tobacco mosaic virus.     

Sesquiterpenes from the leaves of Nicotiana tabacum and their anti-tobacco mosaic virus activity

In searching for more bioactive compounds, phytochemical investigations on the acetone extract of the leaves of Nicotiana tabacum resulted in the isolation of two new sesquiterpenes, nicosesquiterpene A and B(1 and 2), along with four known sesquiterpene derivatives(3–6). Structural elucidation of 1 and 2 was performed by spectral methods, such as HRMS, IR, UV, 1D and 2D NMR spectroscopy. Compounds 1 and 2are the first naturally occurring pterosin-type sesquiterpene bearing an isopropyl moiety. Compounds1–6 were also evaluated for their anti-tobacco mosaic virus(anti-TMV) activity. The results showed that compounds 1 and 2 exhibited high anti-TMV activity with inhibition rates of 36.7% and 45.6%,respectively, which is higher than that of positive control. The other compounds also showed potential activity with inhibition rates in the range of 22.7%–29.2%.     

Synthesis and biological activities of novel 2-amino-1,3-thiazole-4-carboxylic acid derivatives

A series of novel 2-amino-1, 3-thiazole-4-carboxylic acid derivatives were designed and synthesized. Their structures were confirmed by melting points, IR, ¹H NMR, ¹³C NMR, and HRMS or elemental analysis. Biological activities of all title compounds including fungicidal activity and antivirus activity were evaluated systematically. Preliminary bioassays indicated that these compounds exhibited good fungicidal activity at 50 μg/mL, compounds 4b and 4i exhibited over 50% activity against six fungi tested. Most compounds showed good activity against TMV with different models in vivo at 100 μg/mL. Compounds 4c and 4e stood out with high effects against TMV in vivo in all models tested, including protective, inactivative, curative, and inductive activities. These data demonstrate a new strategy for fungi and virus control.     

Synthesis and anti-TMV activity of novel N-(pyrimidin-5-yl)-N'-phenylureas

In order to find novel leading structures of pesticide,a series of N-（pyrimidin-5-yl）-N’-phenylureas（4a-4h） were designed and synthesized from 4-chloro-2-diethylamino-6-methyl-5-nitropyrimidine 1 via substitution,reduction and acylation procedures. Preliminary bioassay showed that all the target compounds processing good anti-TMV（tobacco mosaic virus） activity.Two compounds（4d and 4e） displayed higher activity superior to virazole at a concentration of 5.0×10^-4g/mL.     

Design,synthesis, bioactivity and mechanism of action of novel myricetin derivatives containing amide and hydrazide

A series of myricetin derivatives containing amide and hydrazide were designed and synthesized. All the compounds were characterized by NMR and HRMS. Bioactivity test showed that some of the target compounds had excellent anti-tobacco mosaic virus (TMV) activity. In particular, the median effective concentration (EC₅₀) values of the anti-TMV curative and protective activities of N-(2-(2-(2-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)acetyl)hydrazineyl)-2-oxoethyl)-4-(trifluoromethyl)benzamide (G9) were 202.3 and 164.0 μg/mL respectively, superior to ningnanmycin (329.1, 230.3 μg/mL). Microscale thermophoresis (MST) and molecular docking showed that G9 had an excellent binding affinity with tobacco mosaic virus coat protein (TMV-CP) (K_d = 0.158 ± 0.024 μM), which was better than that of ningnanmycin (K_d = 2.074 ± 0.818 μM). Moreover, there were many interaction forces between G9 and the key amino acid residues of TMV-CP. The chlorophyll content and peroxidase (POD) activity of tobacco leaves treated with G9 increased significantly, indicating that G9 could improve the photosynthesis of tobacco leaves and stimulate the resistance of tobacco leaves to TMV. The insecticidal activity of G9 against Mythimna separata (M. separate) was found to be 95.2% at 200 μg/mL, which was close to bufenozide (100%). The insecticidal activity of myricetin was significantly improved after the introduction of active groups of amide and hydrazide, which could be further explored.     

Bitriazolyl acyclonucleosides with antiviral activity against tobacco mosaic virus

Bitriazolyl acyclonucleosides were synthesized via the Huisgen reaction and then subjected to ammonolysis. The antiviral activity of these nucleosides against tobacco mosaic virus (TMV) was assessed. Like the previously described bitriazolyl compounds, these new bitriazolyl acyclonucleosides were found to show anti-TMV activity. This suggests that the bitriazolyl moieties are important structural features involved in the antiviral activity of these compounds.     

Alkaloids from the roots of Stemona tuberosa and their anti-tobacco mosaic virus activities

Stemtuberlines A (1) and B (2), two new alkaloids with a unique tricyclic pyrrolo [3,2,1-jk]benzazepine-12-one nucleus, three new croomine-type alkaloids, stemtuberlines C-E (3–5), together with seven known ones were isolated from the roots of Stemona tuberosa. The structures of the new alkaloids were elucidated based on a comprehensive spectroscopic data analysis. The absolute configurations of 1 and 2 were determined by quantum ECD calculations. The anti-tobacco mosaic virus activity of the Stemona alkaloids was firstly evaluated and compound 11 exhibited significant anti-tobacco mosaic virus activity with the curative inhibition rate of 84.6% at concentration of 50?μg/mL.