Anthranilic acid derivatives from Inula japonica

Three new anthranilic acid derivatives, N-heneicosanoylanthranilic acid （1b）, N-tricosanoylanthranilic acid （1d）, N-tetracosanoylanthranilic acid （1e）, and two known N-arachidylanthranilic acid （1a） and N-docosanoylanthranilic acid （1c） were isolated from the aerial parts of lnula japonica Thunb. Their structures were established by spectroscopic and chemical methods.

First report of field resistance to cyantraniliprole, a new anthranilic diamide insecticide, on Bemisia tabaciMED in China

The Bemisia tabaci （Gennadius） cryptic species complex comprises important insect pests that cause devastating damage to agricultural crops worldwide. In China, the B. tabaci Mediterranean （MED） （or biotype Q） species is threatening agricul- tural production all over the country as resistance to commonly used insecticides has increased. This situation highlights the need for alternative pest control measures. Cyantraniliprole, a novel anthraniiic diamide insecticide, has been widely employed to control Hemipteran pests. To monitor the levels of resistance to cyantraniliprole in B. tabaci field populations in China, bioassays were conducted for 18 field samples from nine provinces over two years. Compared with median lethal concentration （LC^0） for the MED susceptible strain, all field samples had significantly higher resistance to cyantraniliprole. Furthermore, resistance factors （RFs） increased significantly in samples from Shanxi （from 5.62 in 2015 to 25.81 in 2016）, Hunan （3.30 in 2015 to 20.97 in 2016） and Hubei （from 9.81 in 2015 to 23.91 in 2016） provinces. This study indicates a considerable decrease in the efficacy of cyantraniliprole against B. tabaci and establishes a baseline of susceptibility that could serve as a reference for future monitoring and management of B. tabaci resistance to cyantraniliprole.

2D-QSAR Studies on Anthranilic Acid Derivatives: A Novel Class of Allosteric Inhibitors of Hepatitis C NS5B Polymerase

Quantitative structure activity relationship （QSAR） studies were performed on 45 anthranilic acid derivatives for their potent allosteric inhibition activities of HCV NSSB polymerase. Genetic algorithm based genetic function approximation （GFA） method of variable selection was used to generate the model. Highly statistically significant model with r^2 = 0.966 and r^2cv = 0.951 was obtained when the number of descriptors in the equation was set to 5. High r^2pred value of 0.884 indicates the good predictive power of the best model. Spatial descriptors of radius of gyration （RadOfGration）, molecular volume （Vm）, length of molecule in the z dimension （Shadow-Zlength）, thermodynamic descriptors of the octanol/water partition coefficient （LogP） and molecular refractivity index （MR） showed enormous contributions to HCV NS5B polymerase inhibition. The validation of the model was done by leave-one-out （LOO） test, randomization tests and external test set prediction. The model gives insight on indispensable structural requirements for the activity and can be used to design more potent analogs against HCV NSSB polymerase.

Synthesis, Crystal Structure and Biological Activities of Novel Anthranilic(Isophthalic) Acid Esters

In search of environmentally benign insecticides with high activity, low toxicity and low resistance, a series of novel anthranilic（isophthalic） acid esters was designed and synthesized based on the structure of ryanodine modulating agent. All the compounds were characterized by 1H NMR spectra, elemental analysis or high resolution mass spectrometry（HRMS）. The preliminary results of biological activity assessment indicate that some of the title compounds exhibit certain but unremarkable insecticidal activity against Mythimna separata Walker at 200 mg/L and fungicidal activities against five funguses at 50 mg/L.

Antimicrobial activity and mode of action of terpene linalyl anthranilate against carbapenemase-producing Klebsiella pneumoniae

Mining of plant-derived antimicrobials is the major focus at current to counter antibiotic resistance. This study was conducted to characterize the antimicrobial activity and mode of action of linalyl anthranilate(LNA) against carbapenemase-producing Klebsiella pneumoniae(KPC-KP). LNA alone exhibited bactericidal activity at 2.5%(V/V), and in combination with meropenem(MPM) at 1.25%(V/V). Comparative proteomic analysis showed a significant reduction in the number of cytoplasmic and membrane proteins,indicating membrane damage in LNA-treated KPC-KP cells. Up-regulation of oxidative stress regulator proteins and down-regulation of oxidative stress-sensitive proteins indicated oxidative stress. Zeta potential measurement and outer membrane permeability assay revealed that LNA increases both bacterial surface charge and membrane permeability. Ethidium bromide influx/efflux assay showed increased uptake of ethidium bromide in LNA-treated cells, inferring membrane damage. Furthermore, intracellular leakage of nucleic acid and proteins was detected upon LNA treatment. Scanning and transmission electron microscopies again revealed the breakage of bacterial membrane and loss of intracellular materials. LNA was found to induce oxidative stress by generating reactive oxygen species(ROS) that initiate lipid peroxidation and damage the bacterial membrane. In conclusion, LNA generates ROS, initiates lipid peroxidation, and damages the bacterial membrane, resulting in intracellular leakage and eventually killing the KPC-KP cells.

Down regulation of cotton GbTRP1 leads to accumulation of anthranilates and confers resistance to Verticillium dahliae

Background:Verticillium wilt,caused by Verticillium dahliae,is called a "cancer" disease of cotton.The discovery and identification of defense-related genes is essential for the breeding of Verticillium wilt-resistant varieties.In previous research we identified some possible broad-spectrum resistance genes.Here,we report a tryptophan synthesis-related gene GbTRP1 and its functional analysis in relation to the resistance of cotton to V.dahliae.Results:Expression analysis shows that GbTRP1 is suppressed at 1 h and 6 h post V.dahliae infection,but activated at 12 h and 24 h,and the expression of GbTRP1 is highly induced by treatment with salicylic acid and jasmonic acid.Sub-cellular localization studies show that GbTRP1 is localized in the chloroplast.Suppression of GbTRP1 expression leads to lesion-mimic phenotypes and activates the immune response in cotton by showing enhanced resistance to V.dahliae and B.cinerea.Metabolomic analysis shows that anthranilic compounds significantly accumulated in GbTRP1-silenced plants,and these metabolites can inhibit the growth of V.dahliae and B.cinerea in vitro.Conclusions:Our results show that suppression of GbTRPI expression dramatically activates the immune response and increases resistance of cotton to V.dahliae and B.cinerea,possibly due to the accumulation of anthranilate compounds.This study not only provides genetic resources for disease resistance breeding,but also may provide a basis for new chemical control methods for combatting of fungal disease in cotton.

Continuous Process Optimization and Computational Fluid Dynamics Simulation of a Methyl Anthranilate Jet Reactor

Methyl anthranilate(MA)is an important material for the synthesis of sodium saccharin,but the yield and quality of MA are not stable due to the batch operation conditions.In this study,the optimum conditions obtained by an orthogonal test in a batch reactor were a volume ratio of methanol to amide solution of 5:4,volume ratio of sodium hypochlorite to amide solution of 7:4,Hoffmann degradation reaction duration of 10 min,Hoffmann degradation reaction temperature of 10℃,esterification reaction duration of 10 min,and esterification reaction temperature of 40℃.The working flow velocity and allowable working viscosity range of a Venturi ejector inlet were both determined by a computational fluid dynamics(CFD)simulation.Based on the above experimental data,the continuous operation of the process was tested in a three-stage continuous reactor,which improved the product yield and quality of the process.

Synthesis and Characterization of Poly Anthranilic Acid Metal Nanocomposites

Intrinsically conducting polymer metal nanocomposites were synthesized by polymerising anthranilic acid (PANA) with metal salts like ferric chloride, Zinc oxide and Magnesium oxide by chemical oxidation method. Polyanthranilic acidiron nano composite (PANA-Fe), Polyanthranilic acid-Zinc nano composite(PANA-Zn) and Polyanthranilic acid-magnesium nano composite (PANA-Mg) synthesized were characterised by UV-Visible and FTIR studies. FTIR spectra of polymer-metal nano composites showed peaks in the region between 1690 cm-1 and 1490 cm-1 which corresponds to the deformation in different types of N-H bond. The participation of the -NH group in polymerization was confirmed by the appearance of a peak around 3431 cm-1. Cyclic voltammetric studies revealed the presence of an adherent polymer film on the glassy carbon electrode and showed redox behavior of the polymer metal nanocomposites. The XRD (XRay Diffraction) studies showed a rather more crystalline behaviour of the nano composites and the grain size was calculated using Scherrer’s formula and it was found to be in nano range. SEM (Scanning Electron Microscope) analysis showed a rather mixed crystalline and amorphous behavior. EDAX (Energy Dispersive X Ray Spectroscopy) confirms the incorporation of the metals iron, Zinc and Magnesium in the polymermetal nano composites. The inhibition efficiency of the polymermetal nano composites were calculated for stainless steel in acidic environment using elec-trochemical impedance spectroscopy (EIS) and polarization (Tafel) studies and the prepared PANA-Fe and PANA-Zn nano composites showed effective anti-corrosive behavior on stainless steel in acid medium.

Copolymers of Aniline with O-Anthranilic Acid: Synthesis and Characterization

Chemical copolymerization of aniline with o-anthranilic acid in aqueous 1 M HCl was carried out at different molar ratios of aniline and o-anthranilic acid, and was characterized by FTIR and UVVisible spectroscopy, elemental analysis and electrical conductivity. From FTIR and UV-Visible spectroscopy, we observed that o-anthranilic acid had been introduced into the polymer chain successfully. The percent yield of o-anthanilic acid copolymer with aniline decreases as the percent of aniline increases. An increase in the % C can be observed as the amount of o-anthranilc acid in the copolymer decrease or the amounts of aniline increase. Copolymerization of aniline with o-anthranilic acid would improve the resulting polymer via increasing the molecular weight and the conductivity as well.

Anthranilic diamide compounds:Discovery of tetrachlorantraniliprole

Given the development of insects’resistance and deteriorative ecological environment,the discovery of insecticides with a new mode of action has been proven to be an important tool for comprehensive pest management.Herein,a novel anthranilic diamides containing 3,5-dichloropyridylpyrazole group were designed and synthesized.Their insecticidal potency was assayed against beet armyworm(Spodoptera exigua).Moreover,the structure-activity relationship of these new compounds was also discussed.Of them,compound 15g exhibited potential insecticidal activity.Because of the excellent efficacy against a series of Lepidoptera and low toxicity to mammals,compound 15g,namely tetrachlorantraniliprole,has been developed and launched into the market as an insecticide.

Discovery of Novel Anthranilic Diamide Derivatives Bearing Sulfoximine Group as Potent Insecticide Candidates

The fall armyworm,Spodoptera frugiperda(S.frugiperda),represents the most resistant insect species and poses serious threat to grain yield.Chlorantraniliprole(CHL),which targets the ryanodine receptors(RyRs)in insects,has demonstrated the efficacy in controlling S.frugiperda.Nevertheless,this has led to emerging resistance in several countries.To counter this resistance,a viable approach involves the development of novel compounds that bind against RyRs via distinct binding sites or modes.In this study,a series of 22 novel anthranilic diamide derivatives was designed and synthesized,and their insecticidal activities were evaluated.Most of these derivatives showed moderate to good insecticidal activity against S.frugiperda and Mythimna separata.Time-lapse fluorescence measurements of endoplasmic reticulum luminal calcium revealed that most derivatives elicited cellular responses similar as CHL when assessed on HEK293 cells expressing S.frugiperda ryanodine receptors(SfRyRs).The mode of action of compound 13a was studied and verified on the isolated neurons by calcium imaging technique.Finally,molecular docking analysis was employed to predict the binding mechanism of compound 13a against SfRyRs.Overall,these novel diamide derivatives hold promise as a valuable resource for guiding the future design of insecticidal compounds targeting RyRs.

Design, Synthesis and Biological Activities of Novel Anthranilic Diamide Insecticide Containing Trifluoroethyl Ether

Two series of novel anthranilic diamide insecticide containing trifluoroethyl ether were designed and synthesized, and their structures were characterized by 1H NMR spectroscopy, elemental analysis and single crystal X-ray diffraction analysis. The insecticidal activities of the new compounds were evaluated. The results of bioassays indicated that some of these title compounds exhibited excellent insecticidal activities. The insecticidal activities of compounds 19a, 19b, 19d, 19g, 19k and 19m against oriental armyworm at 2.5 mg·kg-1 were 100%. The larvicidal activities of 19a, 19b, 19c, 19d, 19e, 19g and 19n against diamond-back moth were 100% at 0.1 mg·kg-1. Surprisingly, most of them still exhibited perfect insecticidal activity against diamond-back moth when the concentration was reduced to 0.05 mg·kg-1, which was higher than the commercialized Chlorantraniliprole.

Synthesis, bioactivity, action mode and 3D-QSAR of novel anthranilic diamide derivatives

To study the pesticide effect, action mode, structure-activity relationships (SARs) of anthranilic diamide insecticide and screen highly active pesticides, novel anthranilic diamide derivatives were synthesized.Bioassays indicated that all of the title compounds displayed 100% mortality against diamondback moth and oriental armyworm at 100 mg/L, among which 12 v and 12 w showed 100% insecticidal acitvity at 5 mg/L. Surprisingly compound 12 w exhibited better insecticidal acitvity than commercialized chlorantraniliprole against Pyrausta nubilalis (0.1 mg/L) and Cnaphalocrocis Medinalis (2 mg/L). 3 D-QSAR and SARs statistical analysis revealed that title compounds with R^2 fixed as methoxy had the highest probability possessing high activity. The calcium fluorescence measurements on neurons revealed that E series compounds containing pyrazinyl may have a molecular target different from caffeine on ryanodine receptors rather than the voltage-gated calcium channel present on cytomembran.

Design, Synthesis and Insecticidal Activity of Novel Anthranilic Diamides Containing Oxime Ester and Diacylhydrazine Moieties

Two series of novel anthranilic diamides containing oxime ester and diacylhydrazine moieties were designed and synthesized.Their structures were characterized by melting points,1H NMR,13C NMR and high resolution mass spectrometry（HRMS）.The single crystal structure of compound 7e was determined by X-ray diffraction and their evaluated insecticidal activity against oriental armyworm（Mythimna separata） indicates that some of the compounds exhibited moderate insecticidal activities.Among the 20 compounds,6a and 6b show 100％ larvicidal activity against Mythimna separate Walker at the test concentration of 100 mg/L.

Design, Syntheses and Biological Activities of Novel Anthranilic Diamide Insecticides Containing N-Pyridylpyrazole

In search of environmentally benign insecticides with high activity, low toxicity and low residue, a series of novel anthranilic diamide derivatives containing N-pyridylpyrazole was designed and synthesized. All the compounds were characterized by H NMR spectroscopy and elemental analysis. The single crystal structure of com pound 8j was determined by X-ray diffraction. The insecticidal activities of the new compounds were evaluated. The results show that some compounds exhibited moderate insecticidal activities against Lepidoptera pests. Among this series of compounds, compounds 80 and 8p showed 100% larvicidal activity against Mythimna separate Walker, Plutella xylostella Linnaeus and Laphygma exigua Hubner at a test concentration of 200 mg/kg, which is equal to the commercial chlorantraniliprole.

Synthesis and Biological Activities of Novel Anthranilic Diamides Analogues Containing Benzo[b]thiophene

A series of novel anthranilic diamides analogues containing benzo[b]thiophenyl ring was designed and synthesized. Their structures were characterized by melting points, 1H nuclear magnetic resonance（IH NMR） and high-resolution mass spectrometry（HRMS）. The bioassay tests indicate that their insecticidal activities were weak to moderate. Antibacterial tests indicate that some of the compounds showed favourable activity in vitro against Physa- lospora piricola, Alternaria solani, Cercospora arachidicola, Gibberella sanbinetti and Phytophthora infestans at a dosage of 50 mg/L.

Synthesis, insecticidal activities and SAR studies of novel anthranilic diamides containing trifluoroethoxyl substituent and chiral amino acid moieties

Ryanodine receptors（RyRs） activator has become one class of popular insecticide because of its unique mode of action. In order to find more new RyRs activators as insecticidal agents, a series of 18 novel chiral anthranilic diamides were designed by introducing the D-alanine acid and D-serine acid esters as well as trifluoroethoxyl group into the anthranilic diamide skeleton and synthesized successfully based on anthranilic diamide and FKI-1033 structures. The structures of the title compounds Ia–i and IIa–i were confirmed by melting points,~1H NMR,^（13）C NMR, elemental analysis and specific optical rotation analysis.The preliminary bioassay results indicated that most of the title compounds exhibited considerable larvicidal activities against oriental armyworm at 10 mg/L, especially Ib, Ie and IIh showed remarkable insecticidal activities at 0.5 mg/L. The larvicidal activity against diamondback moth of Ia and IId were 80%and 90% respectively at 0.0001 mg/L, which was similar to that of chlorantraniliprole. The relationship between structure and insecticidal activity was analyzed to reveal a possible co-regulated effect of the chiral amino acid ester, halogen atom or cyano group, and trifluoroethyloxyl group of the skeleton structures of the title compounds, which will provide useful information for guiding the design and discovery of new RyRs activators and insecticidal agrochemicals.

Design,synthesis and insecticidal activity of novel anthranilic diamides with benzyl sulfide scaffold

A series of novel anthranilic diamides with benzyl sulfide scaffold were synthesized,in which N-pyridylpyrazole moiety generally regarded as key pharmacophore was abandoned.The target compounds were characterized by ~1H NMR,^（13）C NMR,^（19）F NMR and HRMS.The preliminary bioassays indicated that half of the title compounds were endowed with good insecticidal activities against armyworm（Mythimna sepatara） at the concentration of 500 mg/L,Exhilaratingly,the synthesized compound 3a was also active against Tetranychus cinnabarinus at 100 mg/L.The difference in activities between the target compounds was influenced by the substituents,which provided some hints for further investigation on structure modifications.

Synthesis and Insecticidal Evaluation of Novel Anthranilic Diamides Derivatives Containing 4-Chlorine Substituted N-Pyridylpyrazole

To search for potent insecticides targeting at ryanodine receptors(RyRs),a series of novel anthranilic diamides analogs containing 4-chlorine N-pyridylpyrazole were designed and synthesized.Their insecticidal activities were evaluated and the preliminary struc ture-activity relationships(SARs)were discussed.The insecticidal results showed that some of the compounds(8a-8h,8m,8n)exhibited good larvicidal activities against oriental armyworm at 2.5 mg·L^(-1),and compound 8m possessed 60%insecticidal activityat 0.5 mg·L^(-1).For diamondback moth,8m exhibited better activity than Chlorantraniliprole at a hundred fold preference.

Synthesis and Biological Evaluation of Novel Anthranilic Diamides Containing N-H/CH3-1H-Pyrazoie

In order to systematically study the structure-activity relationship of anthranilic diamides and develop insecticides with simple structure and high efficiency,a series of novel anthranilic diamides containing N-H/CH3-lH-pyrazole was designed and synthesized.Their chemical structures were characterized by NMR spec-tra,high resolution mass spectrometry(HRMS)or 13C NMR spectra.The preliminary bioassay results indicated that all title compounds displayed moderate insecticidal activity against oriental armyworm(Mythinina separata)at 200 mg/L and ftmgicidal activities against six kinds of fungi at 50 mg/L,especially compound 5i showed 50%insecticidal activity at 25 mg/L.In addition,some compounds exhibited certain antitumor activities.It was demonstrated that the introduction of CH3 group into pyrazole ring was superior to H for the insecticidal activity.