Design, Synthesis, and Insecticidal Activity of Novel Isoxazoline Diacylhydrazine Compounds as GABA Receptor Inhibitors

A series of isoxazoline derivatives containing diacylhydrazine moieties were designed and synthesized as potential insecticides. Most of these derivatives exhibited good insecticidal activities against Plutella xylostella, and some compounds exhibited excellent insecticidal activities against Spodoptera frugiperda. Especially, D14 showed outstanding insecticidal activity against P. xylostella (LC50 = 0.37 μg/mL), which was superior to that of ethiprole (LC50 = 2.84 μg/mL) and tebufenozide (LC50 = 15.3 μg/mL) and similar to that of fluxametamide (LC50 = 0.30 μg/mL). Remarkably, the insecticidal activity of D14 against S. frugiperda (LC50 = 1.72 μg/mL) was superior to that of chlorantraniliprole (LC50 = 3.64 μg/mL) and tebufenozide (LC50 = 60.5 μg/mL) but lower than that of fluxametamide (LC50 = 0.14 μg/mL). The results of electrophysiological experiments, molecular docking, and proteomics experiments indicate that compound D14 acts by interfering with the γ-aminobutyric acid receptor to control pests

Design, Synthesis, and Insecticidal Activity of Novel Isoxazoline Diacylhydrazine Compounds as GABA Receptor Inhibitors

A series of isoxazoline derivatives containing diacylhydrazine moieties were designed and synthesized as potential insecticides. Most of these derivatives exhibited good insecticidal activities against Plutella xylostella, and some compounds exhibited excellent insecticidal activities against Spodoptera frugiperda. Especially, D14 showed outstanding insecticidal activity against P. xylostella (LC50 = 0.37 μg/mL), which was superior to that of ethiprole (LC50 = 2.84 μg/mL) and tebufenozide (LC50 = 15.3 μg/mL) and similar to that of fluxametamide (LC50 = 0.30 μg/mL). Remarkably, the insecticidal activity of D14 against S. frugiperda (LC50 = 1.72 μg/mL) was superior to that of chlorantraniliprole (LC50 = 3.64 μg/mL) and tebufenozide (LC50 = 60.5 μg/mL) but lower than that of fluxametamide (LC50 = 0.14 μg/mL). The results of electrophysiological experiments, molecular docking, and proteomics experiments indicate that compound D14 acts by interfering with the γ-aminobutyric acid receptor to control pests

Synthesis, Antibacterial Activity, and Mechanisms of Novel Indole Derivatives Containing Pyridinium Moieties

The development of effective antibacterial agents equipped with novel action modes and unique skeletons starting from natural compounds serves as an important strategy in the modern pesticide industry. Disclosed here are a series of novel indole derivatives containing pyridinium moieties and their antibacterial activity evaluation against two prevalent phytopathogenic bacteria, Xanthomonas oryzae pv. oryzicola (Xoc) and X. oryzae pv. oryzae (Xoo). A three-dimensional (3D)-QSAR model was adopted to discover higher activity like title compounds based on the Xoc antibacterial activity of the tested compounds. Compound 43 was consequently designed, and it displayed higher antibacterial activity as expected with the half-maximal effective concentration EC50 values of 1.0 and 1.9 μg/mL for Xoo and Xoc, respectively, which were better than those of the commercial drug thiodiazole copper (TC) (72.9 and 87.5 μg/mL). Under greenhouse conditions, the results of a rice in vivo pot experiment indicated that the protective and curative activities of compound 43 against rice bacterial leaf streak (BLS) and rice bacterial blight (BLB) were 45.0 and 44.0% and 42.0 and 39.3%, respectively, which were better than those of the commercial agent thiodiazole copper (38.0 and 37.9%, 38.6 and 37.0%) as well. Scanning electron microscopy images, defense enzyme activity tests, and proteomic techniques were utilized in a preliminary mechanism study, suggesting that compound 43 shall modulate and interfere with the physiological processes and functions of pathogenic bacteria

Coumarin Derivatives Containing Sulfonamide and Dithioacetal Moieties: Design, Synthesis, Antiviral Activity, and Mechanism

Cucumber mosaic virus (CMV) is currently a known plant virus with the most hosts, broadest distribution, and economic hazard. To develop new antiviral drugs against this serious virus, a new range of coumarin derivatives containing sulfonamide and dithioacetal structures were designed and synthesized, and their anti-CMV activities were detected by the half-leaf dead spot method. The results of the biological activity assay showed that most of the compounds exhibited outstanding anti-CMV activity. Especially, compound C23 displayed the optimal in vivo anti-CMV activity, with an EC50 value of 128 μg/mL, which was remarkably better than that of COS (781 μg/mL) and ningnanmycin (436 μg/mL). Excitingly, we found that compound C23 could be a promising plant activator that significantly increased defense-related enzyme activities and the tobacco chlorophyll content. Furthermore, compound C23 enhanced defense responses against viral infection by inducing the abscisic acid (ABA) pathway in tobacco. This work established a basis for multifunction pesticide discovery involving mechanism of action study and structure optimization

Coumarin Derivatives Containing Sulfonamide and Dithioacetal Moieties: Design, Synthesis, Antiviral Activity, and Mechanism

Cucumber mosaic virus (CMV) is currently a known plant virus with the most hosts, broadest distribution, and economic hazard. To develop new antiviral drugs against this serious virus, a new range of coumarin derivatives containing sulfonamide and dithioacetal structures were designed and synthesized, and their anti-CMV activities were detected by the half-leaf dead spot method. The results of the biological activity assay showed that most of the compounds exhibited outstanding anti-CMV activity. Especially, compound C23 displayed the optimal in vivo anti-CMV activity, with an EC50 value of 128 μg/mL, which was remarkably better than that of COS (781 μg/mL) and ningnanmycin (436 μg/mL). Excitingly, we found that compound C23 could be a promising plant activator that significantly increased defense-related enzyme activities and the tobacco chlorophyll content. Furthermore, compound C23 enhanced defense responses against viral infection by inducing the abscisic acid (ABA) pathway in tobacco. This work established a basis for multifunction pesticide discovery involving mechanism of action study and structure optimization

First Discovery of Imidazo[1,2‑<i>a</i>]pyridine Mesoionic Compounds Incorporating a Sulfonamide Moiety as Antiviral Agents

The applications of mesoionic compounds and their analogues as agents against plant viruses remain unexplored. This was the first evaluation of the antiviral activities of mesoionic compounds on this issue. Our study involved the design and synthesis of a series of novel imidazo­[1,2-a]­pyridine mesoionic compounds containing a sulfonamide moiety and the assessment of their antiviral activities against potato virus Y (PVY). Compound A33 was assessed on the basis of three-dimensional quantitative structure–activity relationship (3D-QSAR) model analysis and displayed good curative, protective, and inactivating activity effects against PVY at 500 mg/L, up to 51.0, 62.0, and 82.1%, respectively, which were higher than those of commercial ningnanmycin (NNM, at 47.2, 50.1, and 81.4%). Significantly, defensive enzyme activities and proteomics results showed that compound A33 could enhance the defense response by activating the activity of defense enzymes, inducing the glycolysis/gluconeogenesis pathway of tobacco to resist PVY infection. Therefore, our study indicates that compound A33 could be applied as a potential viral inhibitor

Discovery of Pyrido[1,2‑<i>a</i>]pyrimidine Mesoionic Compounds Containing Benzo[<i>b</i>]thiophene Moiety as Potential Pesticide Candidates

The increasing evolution of insect resistance has made it challenging for traditional insecticides to control the bean aphid (Aphis craccivora Koch). To address this pending issue, a range of pyrido­[1,2-a]­pyrimidine mesoionic compounds containing benzo­[b]­thiophene were designed and synthesized. The biological activity test results of the target compounds indicated that they had moderate to outstanding insecticidal activity against the bean aphid (Aphis craccivora) and moderate insecticidal activity against the white-backed planthopper (Sogatella furcifera). Compound L14 exhibited significant insecticidal activity against A. craccivora, with an LC50 value of 1.82 μg/mL, which was superior to triflumezopyrim (LC50 = 4.76 μg/mL). The results of enzyme activity assay showed that compound L14 had a definite inhibitory effect on ATPase. Moreover, the proteomics and docking findings of compound L14 suggested that it may act on the central nervous system of aphids and interact with nicotinic acetylcholine receptors. Therefore, compound L14 is a potentially novel insecticide candidate for further utilization

First Discovery of Imidazo[1,2‑<i>a</i>]pyridine Mesoionic Compounds Incorporating a Sulfonamide Moiety as Antiviral Agents

The applications of mesoionic compounds and their analogues as agents against plant viruses remain unexplored. This was the first evaluation of the antiviral activities of mesoionic compounds on this issue. Our study involved the design and synthesis of a series of novel imidazo­[1,2-a]­pyridine mesoionic compounds containing a sulfonamide moiety and the assessment of their antiviral activities against potato virus Y (PVY). Compound A33 was assessed on the basis of three-dimensional quantitative structure–activity relationship (3D-QSAR) model analysis and displayed good curative, protective, and inactivating activity effects against PVY at 500 mg/L, up to 51.0, 62.0, and 82.1%, respectively, which were higher than those of commercial ningnanmycin (NNM, at 47.2, 50.1, and 81.4%). Significantly, defensive enzyme activities and proteomics results showed that compound A33 could enhance the defense response by activating the activity of defense enzymes, inducing the glycolysis/gluconeogenesis pathway of tobacco to resist PVY infection. Therefore, our study indicates that compound A33 could be applied as a potential viral inhibitor

Synthesis and antiviral activity of novel thioether derivatives containing 1,3,4-oxadiazole/thiadiazole and emodin moieties

<p>A series of novel thioether derivatives containing 1,3,4-oxadiazole/thiadiazole and emodin moieties were designed and synthesized. The structures of the target compounds were confirmed by ¹H NMR, ¹³C NMR, Infrared, and elemental analysis. The results of bioactivity analysis showed that most of the target compounds exhibited moderate to good antiviral activity against tobacco mosaic virus at a concentration of 500 mg/L. Especially, among the title compounds, <b>Y2</b>, <b>Y8</b>, and <b>Y10</b> possessed appreciable curative activity in vivo, with inhibition rates of 50.51, 52.08, and 54.62%, respectively, which were similar to that of Ningnanmycin (53.40%).</p

Synthesis, Antibacterial Activity, and Mechanisms of Novel Indole Derivatives Containing Pyridinium Moieties

The development of effective antibacterial agents equipped with novel action modes and unique skeletons starting from natural compounds serves as an important strategy in the modern pesticide industry. Disclosed here are a series of novel indole derivatives containing pyridinium moieties and their antibacterial activity evaluation against two prevalent phytopathogenic bacteria, Xanthomonas oryzae pv. oryzicola (Xoc) and X. oryzae pv. oryzae (Xoo). A three-dimensional (3D)-QSAR model was adopted to discover higher activity like title compounds based on the Xoc antibacterial activity of the tested compounds. Compound 43 was consequently designed, and it displayed higher antibacterial activity as expected with the half-maximal effective concentration EC50 values of 1.0 and 1.9 μg/mL for Xoo and Xoc, respectively, which were better than those of the commercial drug thiodiazole copper (TC) (72.9 and 87.5 μg/mL). Under greenhouse conditions, the results of a rice in vivo pot experiment indicated that the protective and curative activities of compound 43 against rice bacterial leaf streak (BLS) and rice bacterial blight (BLB) were 45.0 and 44.0% and 42.0 and 39.3%, respectively, which were better than those of the commercial agent thiodiazole copper (38.0 and 37.9%, 38.6 and 37.0%) as well. Scanning electron microscopy images, defense enzyme activity tests, and proteomic techniques were utilized in a preliminary mechanism study, suggesting that compound 43 shall modulate and interfere with the physiological processes and functions of pathogenic bacteria