Rational design and synthesis of new pyrrolone candidates as prospective insecticidal agents against Culex pipiens L. Larvae.

As a result of its high reactivity, furan-2(3H)-one derivative 2 can be selected as a versatile and suitable candidate for building of novel nitrogen heterocyclic compounds. Consequently, furan-2(3H)-one derivative 2 and some nitrogen nucleophiles were utilized as starting materials for the formation of new pyridazinone and pyrrolone derivatives bearing naphthalene moiety. The continuous buildup of insecticide resistance is the main obstacle facing pest control measures. Pyrrole-based insecticides are a favourable choice due to their unique mode of action and no cross-resistance with traditional neurotoxic insecticides. The larvicidal activities of pyrrolone derivatives were assessed against field and laboratory strains of Culex pipiens larvae in comparison with chlorfenapyr (pyrrole insecticide). Compounds 17 (21.05 µg/mL) > 9 (22.81 µg/mL) > 15 (24.39 µg/mL) > 10 (26.76 µg/mL) > 16 (32.09 µg/mL) were most effective against lab strain of C. pipiens larvae relative to chlorfenapyr (25.43 µg/mL). While in field strain, 17 and 15 were the most toxic compounds followed by 9 > 10 > 16 > 2 with LC50 of 9.87, 10.76, 11.52, 12.68, 15.32 and 18.37 µg/mL, respectively, compared with chlorfenapyr with 14.03 µg/mL. The cytochrome P-450 monooxygenase activities were significantly increased in treated larvae of lab and field strains relative to untreated. The great variations in toxicity of the synthesized compounds were interpreted by structure-activity relationship study. The pyrrolone derivatives are effective against field and insecticide-resistant strains. Therefore, they are considered promising compounds to be integrated into pest management programs.

Novel "Phenyl-Pyrazoline-Oxadiazole" Ternary Substructure Derivatives: Synthesis, Insecticidal Activities, and Structure-Activity Relationship Study.

In recent years, isoxazole insecticides or parasiticides targeting the γ-aminobutyric acid receptor, such as fluralaner or fluxametamide, featured a novel chemical structure and exhibited potent insecticidal activity with no-cross resistance. Thus, many research institutes have tried to modify the structures of these agents to find a new insecticide. Previously, the majority of researchers stuck to the "phenyl-isoxazole-phenyl" structure, making modifications only to other components. In this study, the "phenyl-isoxazole-phenyl" ternary motif was modified for the first time based on bioisosterism theory. A series of new derivatives carrying pyrazoline and 1,3,4-oxadiazole moieties were designed and synthesized to investigate their insecticidal activities against the diamondback moth (Plutella xylostella) and fall armyworm (Spodoptera frugiperda). Preliminary bioassay data showed that some of the target compounds exhibited good insecticidal activities against P. xylostella and S. frugiperda. Especially, compound A21 showed insecticidal activity against P. xylostella (LC50 = 1.2 µg/mL) better than commercial insecticide ethiprole (LC50 = 2.9 µg/mL) but worse than parasiticide fluralaner (LC50 = 0.5 µg/mL). Similarly, compound A21 exhibited insecticidal activity to S. frugiperda (LC50 = 13.2 µg/mL) better than commercial insecticide fipronil (LC50 = 78.8 µg/mL) but worse than fluralaner (LC50 = 0.7 µg/mL). Compound A21 could serve as a potential lead compound to control P. xylostella and S. frugiperda. The three-dimensional quantitative structure-activity relationship model revealed that the further introduction of an electron-donating group in the 2- or 3-site may increase the insecticidal activity of A21. Molecular dynamics simulations showed that the hydrogen bond of A21 and receptor was important for the binding receptor. This study has identified a new substructure called "phenyl-pyrroline-oxadiazole" instead of the previously known "phenyl-isoxazole-phenyl" substructure, offering a useful guide for the design of novel insecticide molecules.

Discovery of the Chlorinated and Ammoniated Derivatives of Vanillin as Potential Insecticidal Candidates Targeting V-ATPase: Structure-Based Virtual Screening, Synthesis, and Bioassay.

Vacuolar-type H+-ATPases (V-ATPases) play a crucial role in the life cycle of agricultural pests and represent a promising target for the development of novel insecticides. In this study, S18, a derivative of vanillin acquired from Specs database using a structure-based virtual screening methodology, was first identified as a V-ATPase inhibitor. It binds to subunit A of the enzyme with a Kd of 1 nM and exhibits insecticidal activity against M. separata. Subsequently, using S18 as the lead compound, a new series of vanillin derivatives were rationally designed and efficiently synthesized. and their biological activities were assessed. Among them, compound 3b-03 showed the strongest insecticidal activity against M. separata by effectively targeting the V-ATPase subunit A with Kd of 0.803 µM. Isothermal titration calorimetric measurements and docking results provided insights into its interaction with subunit A of V-ATPase, which could facilitate future research aimed at the development of novel chemical insecticides.

Design, Synthesis, and Insecticidal Activity of Isoxazoline Derivatives Incorporating an Acylhydrazine Moiety.

The long-term use of agricultural insecticides has led to the development of resistant strains. In this context, the isoxazoline structure has become an active area of pesticide research owing to its wide insecticidal spectrum, nontoxicity to mammals, and lack of cross-resistance with known insecticides. In the present study, based on the discovery of compound G22 in our previous work, a series of novel isoxazoline compounds containing acylhydrazine were designed and synthesized using a scaffold hopping strategy. The insecticidal activities of the target compounds were assessed, and compound L17 (LC50 = 0.489 mg/L) showed insecticidal activity against Spodoptera frugiperda superior to those of the commercial insecticides indoxacarb (LC50 = 3.14 mg/L) and fluralaner (LC50 = 0.659 mg/L). Theoretical calculations indicated that the introduction of acylhydrazine plays an important role in the biological activity of the target compounds. Furthermore, the enzyme-linked immunosorbent assay and molecular docking results indicated that L17 may act on the GABA receptor of the target insect. These results indicated that L17 is a potential candidate compound for controlling S. frugiperda populations in agriculture.

Pyridine Derivatives as Insecticides: Part 6. Design, Synthesis, Molecular Docking, and Insecticidal Activity of 3-(Substituted)methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles Toward Aphis gossypii (Glover, 1887).

Three new series of 3-(substituted)methylthio-4-cyano-5,6,7,8-tetrahydroisoquinolines were designed and synthesized starting from readily available materials, 7-acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8-(4-pyridyl, 3-pyridyl, phenyl, 4-methoxyphenyl, or 4-chlorophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2H)-thiones 2a-e in high yields and very pure states. Thus, compounds 2a-e were reacted with some chloro reagents, namely, N-aryl-2-chloroacetamides 3a-f and N-(naphthalen-2-yl)-2-chloroacetamide (3g) under mild basic conditions to give the first two series of the target compounds, 3-(N-aryl)carbamoylmethylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles 4a-l and 5a-e, respectively. Reaction of compounds 2d,e with ethyl chloroacetate under the same conditions gave the other series, 3-ethoxycarbonyl-methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles 6d,e. Structural formulas of all of the new compounds were elucidated and confirmed by elemental and spectral analyses. The insecticidal activity of all synthesized 5,6,7,8-tetrahydrosoquinolines toward the nymphs and adults of Aphis gossypii were screened. The results revealed the promising insecticidal activity of some tested compounds. Moreover, the structure-activity relationships as well as molecular docking of some representative compounds were evaluated.

Design, synthesis, and evaluation of novel isoxazoline derivatives containing 2-phenyloxazoline moieties as potential insecticides.

Isoxazoline insecticides have shown broad-spectrum insecticidal activity against a variety of insect pests. However, the high toxicity of isoxazoline compounds towards honeybees restricts their application in crop protection. To mitigate this issue, a series of isoxazoline derivatives containing 2-phenyloxazoline were designed and synthesized. Bioassays revealed that several compounds exhibited promising insecticidal activities against Plutella xylostella, with G28 showing particularly excellent insecticidal activity, reflected by an LC50 value of 0.675 mg/L, which is comparable to that of fluxametamide (LC50 = 0.593 mg/L). Furthermore, G28 also exhibited effective insecticidal activity against Solenopsis invicta. Importantly, bee toxicity experiments indicated that G28 had significantly lower acute oral toxicity (LD50 = 2.866 µg/adult) compared to fluxametamide (LD50 = 1.083 µg/adult) and fluralaner (LD50 = 0.022 µg/adult), positioning it as a promising candidate with reduced toxicity to bees. Theoretical simulation further elucidated the reasons for the selective differences in the ability of isoxazoline to achieve higher insecticidal activity while maintaining lower bee toxicity. This research suggests that isoxazoline compounds containing 2-phenyloxazoline group hold potential as new insecticide candidates and offers insights into the development of novel isoxazoline insecticides with both high efficacy and environmental safety.

Cu(II)-tyrosinase enzyme catalyst mediated synthesis of mosquito larvicidal active pyrazolidine-3,5-dione derivatives with molecular docking studies and their ichthyotoxicity analysis.

The objective of this study was to develop pyrazolidine-3,5-dione derivatives with potential as environmentally friendly pesticides for pest control, specifically focusing on their efficacy as larvicidal agents. A novel one-pot synthesis of multicomponent pyrazolidine-3,5-dione derivatives (1a-m) was accomplished via the grindstone method using Cu(II)tyrosinase enzyme as a catalyst under mild reaction conditions, yielding 84%-96%. The synthesised derivatives (1a-m) were characterized using various spectroscopic methods (mass spectrometry, elemental analysis, FT-IR, and 1H and 13C NMR). NMR characterisation using DMSO-d6 as a solvent. The larvicidal and antifeedant activities of the synthesised compounds were screened and in silico computational studies were performed. The larvicidal activity against Culex quinquefasciatus and antifeedant activity against Oreochromis mossambicus were evaluated. Among the synthesised compounds, compound 1c demonstrated superior efficacy (LD50: 9.7 µg/mL) against C. quinquefasciatus compared to permethrin (LD50: 17.1 µg/mL). Regarding antifeedant activity, compounds 1a, 1e, 1f, 1j, and 1k exhibited 100% mortality at 100 µg/mL. Molecular docking analysis was performed to assess the binding capacity of a mosquito odorant-binding protein (3OGN) from Culex quinquefasciatus to compound 1c. The results revealed that compound 1c had a docking score of -10.4 kcal/mol, surpassing that of standard permethrin (-9.5 kcal/mol). Furthermore, DFT calculations were conducted to acquire theoretical data aligned with the experimental FT-IR results. According to experimental research, compound 1c demonstrates promising larvicidal activity against mosquito larvae of C. quinquefasciatus.

Design and Synthesis of Novel Indole-Derived N-Methylcarbamoylguanidinyl Chitinase Inhibitors with Significantly Improved Insecticidal Activity.

Chitinases play an important role in the molting process of insects and are potential targets for the development of green insecticides. Based on the feature that the +1/+2 sites in OfChtI, OfChtII, and OfChi-h have tryptophan residues in mismatch-parallel position, a strategy to introduce indole scaffold into chitinase inhibitors was proposed, and multitarget chitinase inhibitors containing N-methylcarbamoylguanidinyl and indole scaffold were successfully synthesized. The inhibitory activity showed that compound 8u exhibited significant inhibitory activity against OfChtI, OfChtII, and OfChi-h, with IC50 values of 0.7, 0.79, and 0.58 µM, and Ki values of 0.05 ± 0.005, 0.065 ± 0.004, and 0.025 ± 0.006 µM, respectively. In vivo insecticidal activity showed that compounds 8a and 8g exhibited excellent insecticidal activity against Plutella xylostella and Mythimna separata, with LC50 values of 0.79 and 9.17 mg/L against P. xylostella, respectively, and 3.58 and 83.09 mg/L against M. separata, respectively, making them the most potent chitinase inhibitors with in vivo insecticidal activity discovered to date. The inhibition mechanism and binding free energy results suggested that N-methylcarbamoylguanidinyl binds to the -1 catalytic site, while additional interactions acquired by π-π stacking and hydrophobic interactions of the indole scaffold with tryptophan increase the binding affinity of the targets to chitinases. This work provides a new direction for the development of chitinase inhibitors with compounds 8a and 8g potentially serving as promising candidates for pesticide development.

Synthesis, molecular modelling and evaluation of larvicidal efficacy of annulated Benzo[h]chromenes against Culex pipiens L. Larvae.

A new series of substituted benzo[h]chromene, benzochromenopyrimidine, and benzochromenotriazolopyrimidine derivatives were synthesized via chemical transformations of iminonitrile, ethoxymethylene amino, and cyanomethylene functionalities. The chemical structures of the synthesized compounds were assured by spectroscopic data and elemental analysis. The larvicidal efficacy of these compounds against Culex pipiens L. larvae was investigated, revealing potent insecticidal activity, particularly for compounds 6, 10, and 16, exceeding that of the standard insecticide chlorpyrifos. The mode of action of these compounds was explored through molecular docking studies, indicating their potential as acetylcholine esterase (AChE) inhibitors and nicotinic acetylcholine receptors (nAChR) blockers. The structure-activity relationship analysis highlighted the influence of substituents and fused heterocyclic rings on larvicidal potency. These findings suggest that the synthesized compounds hold promise as potential candidates for developing novel and effective mosquito control agents.

Synthesis, Insecticide Evaluation & Molecular Docking Studies of Some New Functionalized Pyrazole Derivatives Against the Cotton Leafworm, Spodoptera littoralis.

5-(Cyanomethyl)-3-((5,5-dimethyl-3-oxocyclohex-1-en-1-yl)amino)-1H-pyrazole-4-carbonitrile (3) is used as a key for the synthesis of arylidenes 5 a-fvia its reaction with some aldehydes 4 a-f. 5-[(5,5-Dimethyl-3-oxocyclohex-1-en-1-yl)amino]-3-(2-imino-2H-chromen-3-yl)-1H-pyrazole-4-carbonitrile (7) was synthesized via the reaction of compound (3) with 2-Hydroxybenzaldehyde in EtOH/piperidine. The target compounds were tested against cotton leafworm larvae in their second and fourth instar. The available data demonstrated that the LC50 values for commercial phenylpyrazole were 3.37 mg/L and 4.55 mg/L for the most affected synthesized compound, 5 b. The chemical structure of compound 5 bhas two cyano moieties, a pyrazole ring and a chlorophenyl, which may be increasing it efficiency. Evaluation of the latent effects of the examined synthesized compounds on various biological parameters, including adult longevity, pupal weight, proportion of normal, deformed pupae, adult emergency, fecundity, and egg hatchability, was done in an additional effort to slightly improve insecticidal compounds. Seven target synthesized compounds were subjected to a molecular docking analysis against glutamate-activated chloride channels. Twelve artificial compounds with the PDB ID of 4COF were subjected to a molecular docking study against the gamma-aminobutyric acid receptor (GABA).

Synthesis, insecticidal Activity, and molecular docking analysis of some benzo[h]quinoline derivatives against Culex pipiens L. Larvae.

Some heterocycles bearing a benzo[h]quinoline moiety were synthesized through treating a 3-((2-chlorobenzo[h]quinolin-3-yl)methylene)-5-(p-tolyl)furan-2(3H)-one with four nitrogen nucleophiles comprising ammonium acetate, benzylamine, dodecan-1-amine, and 1,2-diaminoethane. Also, thiation reactions of furanone and pyrrolinone derivatives were investigated. The insecticidal activity of these compounds against mosquito larvae (Culex pipiens L.) was evaluated. All tested compounds exhibited significant larvicidal activity, surpassing that of the conventional insecticide chlorpyrifos. In silico docking analysis revealed that these compounds may act as acetyl cholinesterase (AChE) inhibitors, potentially explaining their larvicidal effect. Additionally, interactions with other neuroreceptors, such as nicotinic acetylcholine receptor and sodium channel voltage-gated alpha subunit were also predicted. The results obtained from this study reflected the potential of benzo[h]quinoline derivatives as promising candidates for developing more effective and sustainable mosquito control strategies. The ADME (absorption, distribution, metabolism, and excretion) analyses displayed their desirable drug-likeness and oral bioavailability properties.

Synthetic Modification and Insecticidal Activity of 4-epi-cis-Dihydroagarofuran Derivatives.

To synthesize the fundamental framework of dihydroagarofuran, a novel strategy was devised for constructing the C-ring through a dearomatization reaction using 6-methoxy-1-tetralone as the initial substrate. Subsequently, the dihydroagarofuran skeleton was assembled via two consecutive Michael addition reactions. The conjugated diene and trans-dihydroagarofuran skeleton were modified. The insecticidal activities of 33 compounds against Mythimna separata were evaluated. Compounds 11-5 exhibited an LC50 value of 0.378 mg/mL. The activity exhibited a remarkable 29-fold increase compared to positive control Celangulin V, which was widely recognized as the most renowned natural dihydroagarofuran polyol ester insecticidal active compound. Docking experiments between synthetic compounds and target proteins revealed the shared binding sites with Celangulin V. Structure-activity relationship studies indicated that methyl groups at positions C4 and C10 significantly improved insecticidal activity, while ether groups with linear chains displayed enhanced activity; in particular, the allyl ether group demonstrated optimal efficacy. Furthermore, a three-dimensional quantitative structure-activity relationship model was established to investigate the correlation between the skeletal structure and activity. These research findings provide valuable insights for discovering and developing dihydroagarofuran-like compounds.

Pyridine Derivatives as Insecticides. Part 5. New Thieno[2,3-b]pyridines and Pyrazolo[3,4-b]pyridines Containing Mainly Ethyl Nicotinate Scaffold and Their Insecticidal Activity toward Aphis gossypii (Glover,1887).

Ethyl 5-cyano-1,6-dihydro-2-methyl-4-(2'-thienyl)-6-thioxonicotinate (A) was synthesized and reacted with ethyl chloroacetate in the presence of sodium acetate or sodium carbonate to give ethyl 5-cyano-6-((2-ethoxy-2-oxoethyl)thio)-2-methyl-4-(2'-thienyl)nicotinate (1a) or its isomeric thieno[2,3-b]pyridine 2a. 3-Aminothieno[2,3-b]pyridine-2-carboxamide 2b was also synthesized by the reaction of A with 2-chloroacetamide. The reaction of 1a with hydrazine hydrate in boiling ethanol gave acethydrazide 3. Heating ester 1a with hydrazine hydrate under neat conditions afforded 3-amino-1H-pyrazolo[3,4-b]pyridine 10. Compounds 2b, 3, and 10 were used as precursors for synthesizing other new thieno[2,3-b]pyridines and pyrazolo[3,4-b]pyridines containing mainly the ethyl nicotinate scaffold. Structures of all new compounds were confirmed by elemental and spectral analyses. Most of the obtained compounds were evaluated for their insecticidal activity toward the nymphs and adults of Aphis gossypii (Glover,1887). Some compounds such as 4, 9b, and 9c showed promising results. The effect of some sublethal concentrations, less than LC50, of compounds 4, 9b, and 9c on the examined Aphis was subjected to a further study. The results demonstrated that exposure of A. gossypii nymphs to sublethal concentrations of compounds 4, 9b, and 9c had noticeable effects on their biological parameters, i.e., nymphal instar duration, generation time, and adult longevity. The highest concentration C1 of all three compounds increased the nymphal instar duration and generation time and decreased adult longevity and vice versa.

Synthesis and Biological Evaluation of Benzamide Compounds as Insecticides Agents Against Spodoptera Frugiperda (Lepidoptera: Noctuidae).

Due to its severe damage, Spodoptera frugiperda is receiving attention as one of the biggest dangers to world food security. Although there are numerous insecticides that are widely and successfully used to control S. frugiperda, they do not have an immediate effect. In our work focusing for synthesized twelve novel benzamide derivatives and examined their insecticidal effectiveness against S. frugiperda larvae in their second & fourth larvae instars, with the aim of further improving the insecticidal activity based on combination principles. Several spectroscopic methods, including elemental analysis, NMR & infrared spectroscopy, were employed for confirming the structure of the newly designed products. It has been discovered that most compounds show good of promising efficacy. With an LC50 of 24.8 mg/L for larvae in the second instar & 56.2 mg/L for larvae in the fourth instar, compound 23 was the most active. Among all compounds 11, 22 and 20 exhibited excellent results. Furthermore, a number of biological and histopathological properties of the demonstration compounds of the produced goods under laboratory conditions were also examined. This work further demonstrates the anti-proliferation of S. frugiperda and offers fresh ideas for the manufacture of benzamide derivatives.

New prospective insecticidal agents based on thiazolo[4,5-b]quinoxaline derivatives against cotton leafworm Spodoptera litura (Fabricius): Design, synthesis, toxicological, morphology, histological, and biomedical studies.

In this study, a new series of thiazolo[4,5-b]quinoxaline derivatives 3-8 were synthesized by treating 2,3-dichloroquinoxaline with thiosemicarbazone and thiourea derivatives under reflux conditions. The chemical structure of the newly designed derivatives was conducted using spectroscopic techniques. The insecticidal bioassay of the designed derivatives was evaluated against the 2nd and 4th larvae of S. litura after five days as toxicity agents via median lethal concentration (LC50) and the lethal time values (LT50). The results indicated that all the tested compounds had insecticidal effects against both instar larvae of S. litura with variable values. Among them, thiazolo[4,5-b]quinoxaline derivative 3 was the most toxic, with LC50 = 261.88 and 433.68 ppm against 2nd and 4th instar larvae, respectively. Moreover, the thiazolo[4,5-b]quinoxaline derivative 3 required the least time to kill the 50% population (LT50) of 2nd larvae were 20.88, 13.2, and 15.84 hs with 625, 1250, and 2500 ppm, respectively, while for the 4th larval instar were 2.75, 2.08, and 1.76 days with concentrations of 625, 1250, and 2500 ppm, respectively. Larvae's morphological and histological studies for the most active derivative 3 were investigated. According to SEM analysis, the exterior morphology of the cuticle and head capsule was affected. In addition, there were some histological alterations in the cuticle layers and the midgut tissues. Columnar cells began breaking down, and vacuolization occurred in the peritrophic membrane. Moreover, treating 4th S litura larvae hemolymph with compound 3 showed significant changes in biochemical analysis, such as total proteins, GPT, GOT, acetylcholinesterase (AChE), and alkaline phosphatase (AlP). Finally, the toxicity prediction of the most active derivative revealed non-corrosive, non-irritant to the eye, non-respiratory toxicity, non-sensitivity to the skin, non-hepatotoxic, and don't have toxicity on minnow toxicity and T. pyriformis indicating a good toxicity profile for human.

Recent Research Progress in Oxime Insecticides and Perspectives for the Future.

In recent decades, the unique structural attributes and purported insecticidal properties of oximes have garnered increasing attention. A variety of insecticides, encompassing fluxametamide, fluhexafon, and lepimectin, have been synthesized, all of which incorporate oximes. This review endeavors to encapsulate the insecticidal efficacy, structure-activity correlations, and operative mechanisms of oxime-containing compounds. Furthermore, it delves into the conceptual frameworks underpinning the design of innovative oxime-based insecticides, thereby shedding light on prospective advancements in this field.

In-Depth Structural Simplification of Celangulin V: Design, Synthesis, and Biological Activity.

Celangulin V is a novel botanical insecticide with significant bioactivity and a unique molecular target, but its complex polyol ester structure hinders its broader application in agriculture. To discover new analogues of celangulin V with a simpler structure and enhanced biological activities, we initiated a research project aimed at simplifying its structure and assessing insecticidal efficacy. In this study, a series of novel 1-tetralone derivatives were designed via a structure-based rational design approach and synthesized by a facile method. The biological activities of the target compounds were determined against Mythimna separata (M. separata), Plutella xylostella, and Rhopalosiphum padi. The results revealed that most of the synthesized compounds exhibited superior activities compared to celangulin V. Remarkably, the insecticidal activity of compound 6.16 demonstrated 102-fold greater stomach toxicity than celangulin V against M. separata. In addition, certain compounds showed significant contact toxicity against M. separata, a finding not reported previously in the structural optimization studies of celangulin V. Molecular docking analysis illustrated that the binding pocket of compound 6.16 with the H subunit of V-ATPase was the same as celangulin V. This study presents novel insights into the structural optimization of botanical pesticides.

Design, Synthesis, and Acaricidal/Insecticidal Activities of New Phenylpyrazole Derivatives Comprising an Imide Moiety.

Using nicofluprole as the lead compound, we designed and synthesized a series of new phenylpyrazole analogues through substituting the methyl group on the nitrogen atom of the amide with an acyl group. Bioassay results showed that compounds A12-A17 with a 1-cyanocyclopropimide group exhibited outstanding insecticidal activity. The LC50 values for compounds A12-A17 against Tetranychus cinnabarinus ranged from 0.58 to 0.91 mg/L. Compound A15 showed an LC50 value of 0.29 and 3.10 mg/L against Plutella xylostella and Myzus persicae, respectively. Molecular docking indicated the potential binding interactions of compound A15 with a gamma-aminobutyric acid receptor. Additionally, density functional theory calculations implied that the 1-cyanocyclopropimide structure might be essential for its biological activity. Phenylpyrazole derivatives, containing a 1-cyanocyclopropimide fragment, have the potential for further development as potential insecticides.

Synthesis and larvicidal efficacy of pyrazolopyrimidine derivatives conjugated with selenium nanoparticles against Culex pipiens L. and Musca domestica L. larvae.

The synthesized pyrazolopyrimidine derivatives conjugated with selenium nanoparticles were prepared via a reaction of pyrazolone 1 with aryl-aldehyde and malononitrile or 3-oxo-3-phenylpropanenitrile in the presence ammonium acetate or pipridine using an ultrasonic bath as a modified method in the organic synthesis for such materials. The structure of the synthesized compounds was elucidated through various techniques. All the synthesized pyrazolopyrimidines were used in the synthesis of selenium nanoparticles (SeNPs). These nanoparticles were confirmed using UV-spectra, Dynamic Light scattering and (TEM) techniques. The larvicidal efficiency;of the synthesized;compounds; was investigated against some strains such as Culex pipiens;and Musca domestica larvae. Bioassay test showed pyrazolopyrimide derivatives to exhibit an acceptable larvicidal;bio-efficacy. The derivative (3) exhibited;the highest;efficiency for more than; lab strains of both species. Moreover, C. pipiens larvae were more sensitive towards the examined compounds than M. domestica. The field;strain displayed lower affinity for the 2 folds compounds. Some biochemical changes were tracked through analysis of insect main metabolites (protein, lipid and carbohydrate), in addition to measuring the changes in seven enzymes after treatment. Generally, there was a reduction in the protein, lipids and carbohydrates after treatment with all tested compounds. Moreover, a decrement was noticed for acetylcholine esterase and glutathione;S-transferase; enzymes. There was an increment in the acid;phosphatase; and alkaline phosphatase. In addition, there was elevation in Phenoloxidase level but it noticed the declination in both Cytochrome P450 and Ascorbate peroxidase activity after treatment both flies with derivatives of selenium-nanoparticles in both lab and field strain. Generally, the experiments carried out indicate that antioxidant and detoxification enzymes may play a significant role in mechanism of action of our novel nanocompounds. The cytotoxicity of the synthesized compounds and conjugated with SeNPs showed enhanced compatibility with human normal fibroblast cell line (BJ1) with no toxic effect.

Design, Synthesis and Bioactivities of Novel Pyridyl Containing Pyrazole Oxime Ether Derivatives.

In this research, with an aim to develop novel pyrazole oxime ether derivatives possessing potential biological activity, thirty-two pyrazole oxime ethers, including a substituted pyridine ring, have been synthesized and structurally identified through 1H NMR, 13C NMR, and HRMS. Bioassay data indicated that most of these compounds owned strong insecticidal properties against Mythimna separata, Tetranychus cinnabarinus, Plutella xylostella, and Aphis medicaginis at a dosage of 500 µg/mL, and some title compounds were active towards Nilaparvata lugens at 500 µg/mL. Furthermore, some of the designed compounds had potent insecticidal effects against M. separata, T. cinnabarinus, or A. medicaginis at 100 µg/mL, with the mortalities of compounds 8a, 8c, 8d, 8e, 8f, 8g, 8o, 8s, 8v, 8x, and 8z against A. medicaginis, in particular, all reaching 100%. Even when the dosage was lowered to 20 µg/mL, compound 8s also expressed 50% insecticidal activity against M. separata, and compounds 8a, 8e, 8f, 8o, 8v, and 8x displayed more than 60% inhibition rates against A. medicaginis. The current results provided a significant basis for the rational design of biologically active pyrazole oxime ethers in future.