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 and Antibacterial Activities of 2-<i>Oxo</i>-<i>N</i>‑phenylacetamide Derivatives Containing a Dissulfone Moiety Target on Clp

Rice bacterial blight and rice bacterial streak are two serious rice diseases and have caused great harm to the production of rice all over the world. To develop an efficient antibacterial agent with a novel target, a series of novel 2-oxo-N-phenylacetamide derivatives containing a dissulfone moiety were synthesized, and their antibacterial activities were evaluated. Among them, compound D14 exhibited the best antibacterial activities, especially against Xoo and Xoc with EC50 values of 0.63 and 0.79 mg/L, respectively, which were much better than the commercial control of bismerthiazol (BT) (76.59 and 83.35 mg/L, respectively) and thiodiazole copper (TC) (91.72 and 114.00 mg/L, respectively). Meanwhile, compound D14 can interact with a CRP-like protein (Clp) of Pxo99A and show strong binding activity with Xoo-Clp with a Kd value of 0.52 μM, which was far superior to the corresponding Kd values of BT (183.94 μM) and TC (222.58 μM). Treatment of D14 and deletion of the clp gene could significantly reduce the expression of the clp gene and attenuate the virulence of pathogenic bacteria. These results indicated that compound D14 could be used as a potential novel agricultural bactericide and Clp can be used as a target protein for the control of plant bacterial diseases. This work provided reliable support for developing novel antibacterial agents based on Clp as a target protein

Inactivating Activities and Mechanism of Imidazo[1,2‑<i>c</i>]pyrimidin-5(6<i>H</i>)‑one Nucleoside Derivatives Incorporating a Sulfonamide Scaffold

Twenty-eight imidazo[1,2-c]pyrimidin-5(6H)-one nucleoside derivatives incorporating a sulfonamide scaffold with preferable inactivating activities on pepper mild mottle virus (PMMoV) were designed and synthesized. Then, compound B29 with illustrious inactivating activity against PMMoV was received on the basis of the three-dimensional quantitative structure–activity relationship (3D-QSAR) model, with the EC50 of 11.4 μg/mL, which was superior to ningnanmycin (65.8 μg/mL) and template molecule B16 (15.3 μg/mL). Furthermore, (1) transmission electron microscopy (TEM) indicated that B29 could cause severe fracture of virions; (2) microscale thermophoresis (MST) and molecular docking further demonstrated that B29 had faintish binding affinities with PMMoV CPR62A (Kd = 202.84 μM), PMMoV CPL144A (Kd = 141.57 μM), and PMMoV CPR62A,L144A (Kd = 332.06 μM) compared to PMMoV CP (Kd = 4.76 μM); and (3) western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results of pCB-GFP-PMMoV CPR62A, pCB-GFP-PMMoV CPL144A, and pCB-GFP-PMMoV CPR62A,L144A were consistent with MST and confocal. In brief, the above results indicated that the amino acids at positions 62 and 144 of PMMoV CP might be the key amino acid sites of B29 acted on

Synthesis, Antibacterial Activity, and Action Mechanism of Novel Sulfonamides Containing Oxyacetal and Pyrimidine

Bacterial leaf blight (BLB) and bacterial leaf streak (BLS) are two serious bacterial diseases caused by Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), respectively. However, the control of these diseases by conventional pesticides remains challenging due to development of resistances. We aimed to address this pending problem and developed a series of novel pyrimidine sulfonamide derivatives. Structurally, title compounds bear a unique oxyacetal group, which has a proven immune-activating effect. Compound E35 designed based on the 3D-QSAR model was demonstrated as the optimal in vitro activity against Xoo and Xoc, with EC50 values of 26.7 and 30.8 mg/L, respectively, which were higher than the positive controls bismerthiazol (29.9 and 32.7 mg/L) and thiodiazole copper (30.5 and 36.4 mg/L). On the prevention level, the biological activity test showed compound E35 had superior protective activity (43.7%) on BLS to thiodiazole copper (32.1%). The defense enzymes and proteomics results suggested that compound E35 could be a versatile candidate as it improved plant’s resistance to disease

Synthesis, Antibacterial Activity, and Action Mechanism of Novel Sulfonamides Containing Oxyacetal and Pyrimidine

Bacterial leaf blight (BLB) and bacterial leaf streak (BLS) are two serious bacterial diseases caused by Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), respectively. However, the control of these diseases by conventional pesticides remains challenging due to development of resistances. We aimed to address this pending problem and developed a series of novel pyrimidine sulfonamide derivatives. Structurally, title compounds bear a unique oxyacetal group, which has a proven immune-activating effect. Compound E35 designed based on the 3D-QSAR model was demonstrated as the optimal in vitro activity against Xoo and Xoc, with EC50 values of 26.7 and 30.8 mg/L, respectively, which were higher than the positive controls bismerthiazol (29.9 and 32.7 mg/L) and thiodiazole copper (30.5 and 36.4 mg/L). On the prevention level, the biological activity test showed compound E35 had superior protective activity (43.7%) on BLS to thiodiazole copper (32.1%). The defense enzymes and proteomics results suggested that compound E35 could be a versatile candidate as it improved plant’s resistance to disease

Synthesis, Anti-Potato Virus Y Activities, and Interaction Mechanisms of Novel Quinoxaline Derivatives Bearing Dithioacetal Moiety

Quinoxaline and its derivatives are important functional molecules with a broad range of applications. Disclosed here is a design and synthesis of a series of novel quinoxaline derivatives containing dithioacetal moieties as well as their antiviral activities against potato virus Y (PVY). The compound D30 was developed on the basis of the three-dimensional quantitative structure–activity relationship. The anti-PVY activity test showed that the half maximal effective concentration of the anti-PVY protective activity of compound D30 is 197 μg/mL, which was better than the control agents ningnanmycin (423 μg/mL) and xiangcaoliusuobingmi (281 μg/mL). Significantly, compound D30 can increase defense enzyme activity and chlorophyll content, promote photosynthesis by accelerating carbon fixation in tobacco, and further improve plant disease resistance. All of these results suggest that compound D30 could be employed as a lead compound for novel PVY inhibitor discovery

Synthesis, Bioactivities, and Antibacterial Mechanism of 5‑(Thioether)‑<i>N</i>‑phenyl/benzyl-1,3,4-oxadiazole-2-carboxamide/amine Derivatives

1,3,4-Oxadiazole thioethers have shown exciting antibacterial activities; however, the current mechanism of action involving such substances against bacteria is limited to proteomics-mediated protein pathways and differentially expressed gene analysis. Herein, we report a series of novel 1,3,4-oxadiazole thioethers containing a carboxamide/amine moiety, most of which show good in vitro and in vivo bacteriostatic activities. Compounds A10 and A18 were screened through CoMFA models as optimums against Xanthomonas oryzae pv. oryzae (Xoo, EC50 values of 5.32 and 4.63 mg/L, respectively) and Xanthomonas oryzae pv. oryzicola (Xoc, EC50 values of 7.58 and 7.65 mg/L, respectively). Compound A10 was implemented in proteomic techniques and activity-based protein profiling (ABPP) analysis to elucidate the antibacterial mechanism and biochemical targets. The results indicate that A10 disrupts the growth and pathogenicity of Xoc by interfering with pathways associated with bacterial virulence, including the two-component regulation system, flagellar assembly, bacterial secretion system, quorum sensing, ABC transporters, and bacterial chemotaxis. Specifically, the translational regulator (CsrA) and the virulence regulator (Xoc3530) are two effective target proteins of A10. Knocking out the CsrA or Xoc3530 gene in Xoc results in a significant reduction in the motility and pathogenicity of the mutant strains. This study contributes available molecular entities, effective targets, and mechanism basis for the management of rice bacterial diseases

3‑Hydroxy-2-oxindole Derivatives Containing Sulfonamide Motif: Synthesis, Antiviral Activity, and Modes of Action

3-Hydroxy-2-oxindole motif constitutes a core structure in numerous natural products and imparts notable biological activities. Here, we describe the design and synthesis of four series of novel 3-substituted-3-hydroxy-2-oxindole derivatives containing sulfonamide moiety along with their antiviral activities against potato virus Y (PVY). Compound 10b displayed optimal antiviral activity and superior anti-PVY activity compared with the lead compound and commercial Ningnanmycin in terms of curative and protective effects. Additionally, 10b considerably inhibited PVY systemic infection in Nicotiana benthamiana. Physiological and biochemical analyses revealed that the activities of the four crucial defense-related enzymes increased in the tobacco plant following treatment with 10b. RNA-sequencing analysis revealed that 10b substantially induced the upregulation of 38 differentially expressed genes, which were enriched in the photosynthesis pathway. These findings suggest that 10b is a promising antiviral agrochemical that can effectively control PVY infection and trigger plant host immunity to develop virus resistance. This study provides novel molecular entities and ideas for developing new pesticides

New Synthetic Method and Insecticidal Activities of Novel Imidazopyridine Mesoionic Derivatives Containing an Ester Group

To develop novel insecticides with high efficiency, a new mode of action, and safety to nontarget organisms and the environment, a series of imidazopyridine mesoionic compounds containing an ester group have been designed and synthesized via a new synthetic method discovered by our group. The bioactivity results showed that most of the target compounds exhibited significant insecticidal activities against Aphis craccivora, and some of them showed moderate insecticidal activities against Sogatella furcifera. Among them, compounds C2, C4–C11, and D3 showed excellent insecticidal activities against A. craccivora (LC50 values were lower than 4.5 μg/mL), which were superior to those of pymetrozine (LC50 = 6.19 μg/mL) and triflumezopyrim (LC50 = 4.68 μg/mL). Remarkably, the insecticidal activity of compound C9 was 5.9-fold greater than that of triflumezopyrim with an LC50 value of 0.8 μg/mL. Proteomics and molecular docking results indicated that compound C9 may affect the nervous system of A. craccivora and act on nicotinic acetylcholine receptors like triflumezopyrim