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1.
Bioorg Chem ; 150: 107591, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38964147

RESUMO

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.

2.
J Agric Food Chem ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950523

RESUMO

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.

3.
Molecules ; 29(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38930912

RESUMO

The escalating resistance of agricultural pests to chemical insecticides necessitates the development of novel, efficient, and safe biological insecticides. Conus quercinus, a vermivorous cone snail, yields a crude venom rich in peptides for marine worm predation. This study screened six α-conotoxins with insecticidal potential from a previously constructed transcriptome database of C. quercinus, characterized by two disulfide bonds. These conotoxins were derived via solid-phase peptide synthesis (SPPS) and folded using two-step iodine oxidation for further insecticidal activity validation, such as CCK-8 assay and insect bioassay. The final results confirmed the insecticidal activities of the six α-conotoxins, with Qc1.15 and Qc1.18 exhibiting high insecticidal activity. In addition, structural analysis via homology modeling and functional insights from molecular docking offer a preliminary look into their potential insecticidal mechanisms. In summary, this study provides essential references and foundations for developing novel insecticides.


Assuntos
Conotoxinas , Caramujo Conus , Inseticidas , Simulação de Acoplamento Molecular , Conotoxinas/química , Conotoxinas/farmacologia , Conotoxinas/síntese química , Inseticidas/química , Inseticidas/síntese química , Inseticidas/farmacologia , Animais , Caramujo Conus/química , Sequência de Aminoácidos , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/síntese química , Técnicas de Síntese em Fase Sólida/métodos
4.
J Agric Food Chem ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38912665

RESUMO

To discover novel natural product-based insecticides, a series of (+)-nootkatone-based amine derivatives 3a-t were prepared and evaluated for their insecticidal activities against Mythimna separata Walker, Myzus persicae Sulzer, and Plutella xylostella Linnaeus. Insecticidal assays showed that most of the title (+)-nootkatone derivatives exhibited stronger insecticidal activities against three insect pests than the precursor (+)-nootkatone after the introduction of amine groups on the parent (+)-nootkatone. Compounds 3a, 3d, 3h, 3m, 3n, 3p, and 3r displayed more promising growth inhibitory (GI) effect against M. separata than the commercially available botanical insecticide toosendanin. Compound 3o exhibited the most potent aphicidal activity with an LD50 value of 0.011 µg/larvae, which was 2.09-fold higher than the positive control rotenone. Additionally, compounds 3g and 3n showed more promising larvicidal activity against P. xylostella with LC50 values of 260 and 230 mg/L, respectively, superior to that of rotenone (460 mg/L). Moreover, derivatives 3g and 3n exhibited better control efficacy toward P. xylostella than rotenone under greenhouse conditions. Preliminary mechanistic studies revealed that derivative 3n could inhibit the activity of glutathione S-transferase (GST) in P. xylostella and thus exerted larvicidal activity, and molecular docking further demonstrated that 3n could interact well with some amino acid residues of GST. Finally, the toxicity assay suggested that derivatives 3g and 3n were relatively less toxic to nontarget organisms. These findings will provide insights into the development of (+)-nootkatone derivatives as green pesticides.

5.
Chem Biodivers ; : e202400948, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899798

RESUMO

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.

6.
Pestic Biochem Physiol ; 202: 105917, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879319

RESUMO

Owing to their beneficial functional capabilities, essential oils were largely used. However, their low aqueous solubility, instability, and high volatility urged scientists to their encapsulation with cyclodextrins (CDs) to tackle their shortcomings. In this study, the co-precipitation method was used to prepare ß-CD/Eucalyptus globulus essential oil (EGEO) inclusion complexes (ICs). ß-CD/EGEO ICs were prepared at ratios (w:w) 1:2 and 1:4 with an encapsulation efficiency of 93 and 96%, respectively. The ICs characterization using the Fourier transform Infrared spectroscopy, differential scanning calorimetry, X-ray powder diffraction, Dynamic Light Scattering, and Laser Doppler Velocimetry confirmed the formation of ß-CD/EGEO ICs. The insecticidal activity of the free EGEO and ICs was explored and displayed that the complex ß-CD/EGEO 1:4 had the highest activity with the lowest LC50 against Ephestia kuehniella larvae (5.03 ± 1.16 mg/g) when compared to the free oil (8.38 ± 1.95 mg/g). Molecular docking simulations stipulated that the compound α-Bisabolene epoxide had the best docking score (ΔG = -7.4 Kcal/mol) against the selected insecticidal target α-amylase. Additionally, toxicity evaluation of the studied essential oil suggested that it could be safely used as a potent bioinsecticide as compared to chemical insecticides. This study reveals that the formation of ß-CD/EGEO ICs enhanced the oil activity and stability and could be a promising and safe tool to boost its application in food or pharmaceutical fields.


Assuntos
Eucalyptus , Inseticidas , Larva , Simulação de Acoplamento Molecular , Óleos Voláteis , beta-Ciclodextrinas , Animais , Inseticidas/química , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Eucalyptus/química , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacologia , Besouros/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
7.
Fungal Biol ; 128(4): 1827-1835, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38876535

RESUMO

Metarhizium rileyi has a broad biocontrol spectrum but is highly sensitive to abiotic factors. A Colombian isolate M. rileyi Nm017 has shown notorious potential against Helicoverpa zea. However, it has a loss of up to 22 % of its conidial germination after drying, which limits its potential as a biocontrol agent and further commercialization. Conidial desiccation resistance can be enhanced by nutritional supplements, which promotes field adaptability and facilitates technological development as a biopesticide. In this study, the effect of culture medium supplemented with linoleic acid on desiccation tolerance in Nm017 conidia was evaluated. Results showed that using a 2 % linoleic acid-supplemented medium increased the relative germination after drying by 41 % compared to the control treatment, without affecting insecticidal activity on H. zea. Also, the fungus increased the synthesis of trehalose, glucose, and erythritol during drying, independently of linoleic acid use. Ultrastructural analyses of the cell wall-membrane showed a loss of thickness by 22 % and 25 %, in samples obtained from 2 % linoleic acid supplementation and the control, respectively. Regarding its morphological characteristics, conidia inner area from both treatments did not change after drying. However, conidia from the control had a 24 % decrease in length/width ratio, whereas there was no alteration in conidia from acid linoleic. The average value of dry conidia elasticity coefficient from linoleic acid treatment was 200 % above the control. Medium supplementation with linoleic acid is a promising fermentation strategy for obtaining more tolerant conidia without affecting production and biocontrol parameters, compatible solutes synthesis, or modifying its cell configuration.


Assuntos
Meios de Cultura , Ácido Linoleico , Metarhizium , Esporos Fúngicos , Metarhizium/fisiologia , Metarhizium/efeitos dos fármacos , Metarhizium/crescimento & desenvolvimento , Ácido Linoleico/metabolismo , Ácido Linoleico/farmacologia , Esporos Fúngicos/efeitos dos fármacos , Esporos Fúngicos/crescimento & desenvolvimento , Meios de Cultura/química , Animais , Dessecação , Controle Biológico de Vetores , Colômbia , Mariposas/microbiologia
8.
Plant Sci ; 346: 112161, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38879177

RESUMO

Paper mulberry (Broussonetia papyrifera) is a fast-growing tree known for its tolerance to diverse biotic and abiotic stresses. To explore genes combating Verticillium wilt, a devasting and formidable disease damage to cotton and many economically significant crops, we purified an antifungal protein, named BpAFP, from the latex of paper mulberry. Based on peptide fingerprint, we cloned the full cDNA sequence of BpAFP and revealed that BpAFP belongs to Class I chitinases, sharing 74 % identity with B. papyrifera leaf chitinase, PMAPII. We further introduced BpAFP into Arabidopsis, tobacco, and cotton. Transgenic plants exhibited significant resistance to Verticillium wilt. Importantly, BpAFP also demonstrated insecticidal activity against herbivorous pests, Plutella xylostella, and Prodenia litura, when feeding the larvae with transgenic leaves. Our finding unveils a dual role of BpAFP in conferring resistance to both plant diseases and lepidopterous pests.

9.
J Agric Food Chem ; 72(27): 15077-15091, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38920088

RESUMO

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.


Assuntos
Inseticidas , Oximas , Inseticidas/química , Inseticidas/farmacologia , Inseticidas/síntese química , Oximas/química , Animais , Relação Estrutura-Atividade , Estrutura Molecular , Insetos/efeitos dos fármacos , Insetos/química
10.
J Agric Food Chem ; 72(27): 15142-15150, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38926152

RESUMO

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.


Assuntos
Desenho de Fármacos , Inseticidas , Simulação de Acoplamento Molecular , Mariposas , Inseticidas/química , Inseticidas/farmacologia , Inseticidas/síntese química , Animais , Mariposas/efeitos dos fármacos , Relação Estrutura-Atividade , Afídeos/efeitos dos fármacos , Estrutura Molecular , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Proteínas de Insetos/química , Haptenos
11.
J Agric Food Chem ; 72(27): 15276-15283, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38943575

RESUMO

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.


Assuntos
Acaricidas , Desenho de Fármacos , Inseticidas , Simulação de Acoplamento Molecular , Pirazóis , Animais , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Acaricidas/química , Acaricidas/farmacologia , Acaricidas/síntese química , Inseticidas/química , Inseticidas/farmacologia , Inseticidas/síntese química , Relação Estrutura-Atividade , Imidas/química , Imidas/farmacologia , Imidas/síntese química , Afídeos/efeitos dos fármacos , Mariposas/efeitos dos fármacos , Tetranychidae/efeitos dos fármacos , Estrutura Molecular
12.
Molecules ; 29(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731415

RESUMO

Investigations have shown that storage bugs seriously harm grains during storage. In the interim, essential oils (EOs) have been proven to be a good botanical pesticide. The anti-Lasioderma serricorne properties of Elsholtzia ciliata essential oil, which was obtained by steam distillation, were evaluated using DL-limonene, carvone, and their two optical isomer components using contact, repelling, and fumigation techniques. Simultaneously, the fumigation, contact, and repellent activities of carvone and its two optical isomers mixed with DL-limonene against L. serruricorne were evaluated. The results showed that E. ciliata, its main components (R-carvone, DL-limonene), and S-carvone exhibited both fumigations (LC50 = 14.47, 4.42, 20.9 and 3.78 mg/L) and contact (LD50 = 7.31, 4.03, 28.62 and 5.63 µg/adult) activity against L.serricorne. A binary mixture (1:1) of R-carvone and DL-limonene displayed an obvious synergistic effect. A binary mixture (1:1) of carvone and its two optical isomers exhibited an obvious synergistic effect, too. Furthermore, the repellent activity of the EO, carvone, and its two optical isomers, DL-limonene, and a combination of them varied. To stop insect damage during storage, E. ciliata and its components can be utilized as bio-insecticides.


Assuntos
Inseticidas , Lamiaceae , Óleos Voláteis , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Lamiaceae/química , Animais , Inseticidas/química , Inseticidas/farmacologia , Limoneno/química , Limoneno/farmacologia , Repelentes de Insetos/química , Repelentes de Insetos/farmacologia , Monoterpenos Cicloexânicos/química , Monoterpenos Cicloexânicos/farmacologia , Sinergismo Farmacológico , Fumigação
13.
J Agric Food Chem ; 72(21): 11949-11957, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38757770

RESUMO

As the first marketed phenylpyrazole insecticide, fipronil exhibited remarkable broad-spectrum insecticidal activity. However, it poses a significant threat to aquatic organisms and bees due to its high toxicity. Herein, 35 phenylpyrazole derivatives containing a trifluoroethylthio group on the 4 position of the pyrazole ring were designed and synthesized. The predicted physicochemical properties of all of the compounds were within a reasonable range. The biological assay results revealed that compound 7 showed 69.7% lethality against Aedes albopictus (A. albopictus) at the concentration of 0.125 mg/L. Compounds 7, 7g, 8d, and 10j showed superior insecticidal activity for the control of Plutella xylostella (P. xylostella). Notably, compound 7 showed similar insecticidal activity against Aphis craccivora (A. craccivora) compared with fipronil. Potential surface calculation and molecular docking suggested that different lipophilicity and binding models to the Musca domestica (M. domestica) gamma-aminobutyric acid receptors may be responsible for the decreased activity of the tested derivatives. Toxicity tests indicated that compound 8d (LC50 = 14.28 mg/L) induced obviously 14-fold lower toxicity than fipronil (LC50 = 1.05 mg/L) on embryonic-juvenile zebrafish development.


Assuntos
Aedes , Desenho de Fármacos , Moscas Domésticas , Inseticidas , Simulação de Acoplamento Molecular , Pirazóis , Animais , Inseticidas/química , Inseticidas/síntese química , Inseticidas/farmacologia , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Aedes/efeitos dos fármacos , Aedes/crescimento & desenvolvimento , Relação Estrutura-Atividade , Moscas Domésticas/efeitos dos fármacos , Moscas Domésticas/crescimento & desenvolvimento , Afídeos/efeitos dos fármacos , Afídeos/crescimento & desenvolvimento , Mariposas/efeitos dos fármacos , Mariposas/crescimento & desenvolvimento , Estrutura Molecular , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Peixe-Zebra/embriologia
14.
J Agric Food Chem ; 72(21): 11968-11979, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38759145

RESUMO

With the aim of identifying novel neonicotinoid insecticides with low bee toxicity, a series of compounds bearing thiazolidine moiety, which has been shown to be low bee toxic, were rationally designed through substructure splicing strategy and evaluated insecticidal activities. The optimal compounds A24 and A29 exhibited LC50 values of 30.01 and 17.08 mg/L against Aphis craccivora, respectively. Electrophysiological studies performed on Xenopus oocytes indicated that compound A29 acted on insect nAChR, with EC50 value of 50.11 µM. Docking binding mode analysis demonstrated that A29 bound to Lymnaea stagnalis acetylcholine binding protein through H-bonds with the residues of D_Arg55, D_Leu102, and D_Val114. Quantum mechanics calculation showed that A29 had a higher highest occupied molecular orbit (HOMO) energy and lower vertical ionization potential (IP) value compared to the high bee toxic imidacloprid, showing potentially low bee toxicity. Bee toxicity predictive model also indicated that A29 was nontoxic to honeybees. Our present work identified an innovative insecticidal scaffold and might facilitate the further exploration of low bee toxic neonicotinoid insecticides.


Assuntos
Inseticidas , Neonicotinoides , Tiazolidinas , Animais , Inseticidas/química , Inseticidas/toxicidade , Abelhas/efeitos dos fármacos , Neonicotinoides/química , Neonicotinoides/toxicidade , Tiazolidinas/química , Tiazolidinas/toxicidade , Simulação de Acoplamento Molecular , Proteínas de Insetos/genética , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Proteínas de Insetos/toxicidade , Afídeos/efeitos dos fármacos , Afídeos/genética , Relação Estrutura-Atividade , Estrutura Molecular , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/química
15.
J Agric Food Chem ; 72(20): 11341-11350, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38713071

RESUMO

Insect neuropeptides play an essential role in regulating growth, development, reproduction, nerve conduction, metabolism, and behavior in insects; therefore, G protein-coupled receptors of neuropeptides are considered important targets for designing green insecticides. Cockroach-type allatostatins (ASTs) (FGLamides allatostatins) are important insect neuropeptides in Diploptera punctata that inhibit juvenile hormone (JH) synthesis in the corpora allata and affect growth, development, and reproduction of insects. Therefore, the pursuit of novel insecticides targeting the allatostatin receptor (AstR) holds significant importance. Previously, we identified an AST analogue, H17, as a promising candidate for pest control. Herein, we first modeled the 3D structure of AstR in D. punctata (Dippu-AstR) and predicted the binding mode of H17 with Dippu-AstR to study the critical interactions and residues favorable to its bioactivity. Based on this binding mode, we designed and synthesized a series of H17 derivatives and assessed their insecticidal activity against D. punctata. Among them, compound Q6 showed higher insecticidal activity than H17 against D. punctata by inhibiting JH biosynthesis, indicating that Q6 is a potential candidate for a novel insect growth regulator (IGR)-based insecticide. Moreover, Q6 exhibited insecticidal activity against Plutella xylostella, indicating that these AST analogs may have a wider insecticidal spectrum. The underlying mechanisms and molecular conformations mediating the interactions of Q6 with Dippu-AstR were explored to understand its effects on the bioactivity. The present work clarifies how a target-based strategy facilitates the discovery of new peptide mimics with better bioactivity, enabling improved IGR-based insecticide potency in sustainable agriculture.


Assuntos
Proteínas de Insetos , Inseticidas , Neuropeptídeos , Peptidomiméticos , Inseticidas/química , Inseticidas/farmacologia , Inseticidas/síntese química , Animais , Neuropeptídeos/química , Neuropeptídeos/farmacologia , Neuropeptídeos/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Peptidomiméticos/química , Peptidomiméticos/farmacologia , Peptidomiméticos/síntese química , Desenho de Fármacos , Hormônios Juvenis/química , Hormônios Juvenis/farmacologia , Hormônios Juvenis/metabolismo , Baratas/efeitos dos fármacos , Baratas/química
16.
J Agric Food Chem ; 72(20): 11331-11340, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38721769

RESUMO

Research on mesoionic structures in pesticide design has gained significant attention in recent years. However, the 1-position of pyridino[1,2-a]pyrimidine is usually designed with 2-chlorothiazole, 2-chloropyridine, or cyano moieties commonly found in neonicotinoid insecticides. In order to enrich the available pharmacophore library, here, we disclose a series of new pyridino[1,2-a]pyrimidine mesoionics bearing indole-containing substituents at the 1-position. Most of these target compounds are confirmed to have good insecticidal activity against aphids through bioevaluation. In addition, a three-dimensional structure-activity relationship model is established to allow access to optimal compound F45 with an LC50 value of 2.97 mg/L. This value is comparable to the property achieved by the positive control triflumezopyrim (LC50 = 2.94 mg/L). Proteomics and molecular docking analysis suggest that compound F45 has the potential to modulate the functioning of the aphid nervous system through its interaction with neuronal nicotinic acetylcholine receptors. This study expands the existing pharmacophore library for the future development of new mesoionic insecticides based on 1-position modifications of the pyridino[1,2-a]pyrimidine scaffold.


Assuntos
Afídeos , Desenho de Fármacos , Indóis , Inseticidas , Simulação de Acoplamento Molecular , Pirimidinas , Inseticidas/química , Inseticidas/síntese química , Inseticidas/farmacologia , Animais , Pirimidinas/química , Pirimidinas/farmacologia , Pirimidinas/síntese química , Afídeos/efeitos dos fármacos , Indóis/química , Indóis/farmacologia , Indóis/síntese química , Relação Estrutura-Atividade , Estrutura Molecular , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/química , Receptores Nicotínicos/efeitos dos fármacos
17.
Chem Biodivers ; : e202400776, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733168

RESUMO

A significant reason for developing innovative insecticidal active agents is the exponential rise in resistance to traditional chemical pesticides. Exploring new classes of insecticidal compounds with distinct mechanisms of action is one way to address this difficulty. So that, novel aryl thioamides derivatives 3-15 has been synthesized viaone-pot, three-component reaction of aroyl chloride, ammonium thiocyanate, and aromatic amines in dry acetone. The newly synthesized compounds' structures were validated by various spectroscopic methods, including elemental analysis, 1H-NMR, 13C NMR, and infrared spectroscopy. Under laboratory circumstances, the synthesized compounds showed good and broad-spectrum insecticidal activities toward S. littorali. When compared to other synthetic target compounds, 2,4-dichloro-N-[(3-fluorophenyl)carbamothioyl]benzamide 11, 2,4-dichloro-N-[(3-fluorophenyl)carbamothioyl]benzenecarbothioamide 13 showed good insecticidal activity, with 46.33 mg/L and LC50 values of 49.25 mg/L for 2nd instar larvae. Furthermore, the compound 3 was the least toxic in controlling the second and fourth instar larvae of S. littoralis on tomato leaves. Additionally, several histopathological and biochemical features of the some synthesized compounds under laboratory circumstances were also examined.

18.
J Agric Food Chem ; 72(23): 12956-12966, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38820064

RESUMO

Bees, one of the most vital pollinators in the ecosystem and agriculture, are currently threatened by neonicotinoids. To explore the molecular mechanisms of neonicotinoid toxicity to bees, the different binding modes of imidacloprid, thiacloprid, and flupyradifurone with nicotinic acetylcholine receptor (nAChR) α1ß1 and cytochrome P450 9Q3 (CYP9Q3) were studied using homology modeling and molecular dynamics simulations. These mechanisms provided a basis for the design of compounds with a potential low bee toxicity. Consequently, we designed and synthesized a series of triazinone derivatives and assessed their bioassays. Among them, compound 5a not only displayed substantially insecticidal activities against Aphis glycines (LC50 = 4.40 mg/L) and Myzus persicae (LC50 = 6.44 mg/L) but also had low toxicity to Apis mellifera. Two-electrode voltage clamp recordings further confirmed that compound 5a interacted with the M. persicae nAChR α1 subunit but not with the A. mellifera nAChR α1 subunit. This work provides a paradigm for applying molecular toxic mechanisms to the design of compounds with low bee toxicity, thereby aiding the future rational design of eco-friendly nicotinic insecticides.


Assuntos
Proteínas de Insetos , Inseticidas , Neonicotinoides , Receptores Nicotínicos , Abelhas/efeitos dos fármacos , Animais , Inseticidas/química , Inseticidas/toxicidade , Neonicotinoides/química , Neonicotinoides/toxicidade , Neonicotinoides/metabolismo , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/química , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Afídeos/efeitos dos fármacos , Nitrocompostos/química , Nitrocompostos/toxicidade , Desenho de Fármacos , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/química , Simulação de Dinâmica Molecular , Ligação Proteica , Tiazinas
19.
Chem Biodivers ; : e202400929, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661022

RESUMO

In order to explore novel natural product-based insecticidal agent, two important intermediates (2 and 3) and 4-acyloxy-2'-bromo-6'-chloropodophyllotoxin derivatives (4 a-f and 5 a-f) were designed and prepared, and their structures were confirmed by 1H-NMR, 13C NMR, HRMS, ESI-MS, optical rotation and melting point (mp). The stereochemical configuration of compound 4 b was unambiguously confirmed by single-crystal X-ray diffraction. Moreover, we evaluated the insecticidal activity of target compounds 4 a-f and 5 a-f against a serious agricultural pest of Mythimna separata by using the leaf-dipping method. Among all tested compounds, compounds 4 d, 5 d and 5 f exhibited stronger insecticidal activity with a final mortality rate exceeding 60 %. Especially compound 5 d exhibited the best insecticidal activity, with a final mortality rate of 74.1 %. It has been proven that introducing bromine or chlorine atoms at the C-2', C-2' and C-6' positions of the E ring of podophyllotoxin can produce more potent compounds. In addition, the configuration of the C-4 position is important for insecticidal activity, and 4ß-configuration is optimal. This will pave the way for further design, structural modification, and development of derivatives of podophyllotoxin as insecticidal agents.

20.
Molecules ; 29(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38611746

RESUMO

Spodoptera frugiperda, the fall armyworm (FAW), is a highly invasive polyphagous insect pest that is considered a source of severe economic losses to agricultural production. Currently, the majority of chemical insecticides pose tremendous threats to humans and animals besides insect resistance. Thus, there is an urgent need to develop new pest management strategies with more specificity, efficiency, and sustainability. Chitin-degrading enzymes, including chitinases, are promising agents which may contribute to FAW control. Chitinase-producing microorganisms are reported normally in bacteria and fungi. In the present study, Serratia marcescens was successfully isolated and identified from the larvae of Spodoptera frugiperda. The bacterial strain NRC408 displayed the highest chitinase enzyme activity of 250 units per milligram of protein. Subsequently, the chitinase gene was cloned and heterologously expressed in E. coli BL21 (DE3). Recombinant chitinase B was overproduced to 2.5-fold, driven by the T7 expression system. Recombinant chitinase B was evaluated for its efficacy as an insecticidal bioagent against S. frugiperda larvae, which induced significant alteration in subsequent developmental stages and conspicuous malformations. Additionally, our study highlights that in silico analyses of the anticipated protein encoded by the chitinase gene (ChiB) offered improved predictions for enzyme binding and catalytic activity. The effectiveness of (ChiB) against S. frugiperda was evaluated in laboratory and controlled field conditions. The results indicated significant mortality, disturbed development, different induced malformations, and a reduction in larval populations. Thus, the current study consequently recommends chitinase B for the first time to control FAW.


Assuntos
Quitinases , Inseticidas , Animais , Humanos , Quitinases/genética , Quitinases/farmacologia , Larva , Serratia marcescens/genética , Zea mays , Spodoptera , Escherichia coli , Clonagem Molecular , Produtos Agrícolas , Inseticidas/farmacologia
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