Synthesis of Novel Antiviral Ferulic Acid–Eugenol and Isoeugenol Hybrids Using Various Link Reactions

To develop novel antiviral agents, some novel conjugates between ferulic acid and eugenol or isoeugenol were designed and synthesized by the link reaction. The antiviral activities of compounds were evaluated using the half leaf dead spot method. Bioassay results showed acceptable antiviral activities of some conjugates against the tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). Compounds A9, A10, E1, and E4 showed remarkable curative, protective, and inactivating effects on TMV and CMV at 500 μg mL–1. Notably, these compounds exhibited excellent protective effects on TMV and CMV. The EC50 values of compounds A9, A10, E1, and E4 against TMV were 180.5, 169.5, 211.4, and 135.5 μg mL–1, respectively, and those against CMV were 210.5, 239.1, 218.4, and 178.6 μg mL–1, respectively, which were superior to those of ferulic acid (471.5 and 489.2 μg mL–1), eugenol (456.3 and 463.2 μg mL–1), isoeugenol (478.4 and 487.5 μg mL–1), and ningnanmycin (246.5 and 286.6 μg mL–1). Then, the antiviral mechanisms of compound E4 were investigated by determining defensive enzyme activities and multi-omics analysis. The results indicated that compound E4 resisted the virus infection by enhancing defensive responses via inducing the accumulation of secondary metabolites from the phenylpropanoid biosynthesis pathway in tobacco

DataSheet1_Active Metabolites From the Endophyte Paenibacillus polymyxa Y-1 of Dendrobium nobile for the Control of Rice Bacterial Diseases.docx

Microbial bactericides have been a research hotspot in recent years. In order to find new microbial fungicides for preventing and treating rice bacterial diseases, Paenibacillus polymyxa Y-1 (P. polymyxa Y-1) was isolated from Dendrobium nobile in this study, and the optimal medium was selected by a single-factor experiment, and then eight metabolites were isolated from P. polymyxa Y-1 fermentation broth by bioactivity tracking separation. The bioassay results showed that 2,4-di-tert-butylphenol, N-acetyl-5-methoxytryptamine, and P-hydroxybenzoic acid have good antibacterial activity against Xanthomonas oryzae pv. Oryzicola (Xoo) and Xanthomonas oryzae pv. oryzae (Xoc), with 50% effective concentration values of 49.45 μg/ml, 64.22 μg/ml, and 16.32 μg/ml to Xoo, and 34.33 μg/ml, 71.17 μg/ml, and 15.58 μg/ml to Xoc, respectively, compared with zhongshengmycin (0.42 and 0.82 μg/ml, respectively) and bismerthiazol (85.64 and 92.49 μg/ml, respectively). In vivo experiments found that 2,4-di-tert-butylphenol (35.9 and 35.4%, respectively), N-acetyl-5-methoxytryptamine (42.9 and 36.7%, respectively), and P-hydroxybenzoic acid (40.6 and 36.8%, respectively) demonstrated excellent protective and curative activity against rice bacterial leaf blight, which were better than that of zhongshengmycin (38.4 and 34.4%, respectively). In addition, after 2,4-di-tert-butylphenol, N-acetyl-5-methoxytryptamine, and P-hydroxybenzoic acid acted on rice, SOD, POD, and CAD defense enzymes increased under the same condition. In conclusion, these results indicated that the activity and mechanism research of new microbial pesticides were helpful for the prevention and control of rice bacterial diseases.</p

Table_2_Polymyxin B1 and E2 From Paenibacillus polymyxa Y-1 for Controlling Rice Bacterial Disease.docx

To discover novel microbial pesticide for controlling rice bacterial disease, polymyxin B1 and E2 were firstly isolated from the supernatant of fermentation broth of Paenibacillus polymyxa Y-1 by bioactivity tracking separation. It is shown that polymyxin B1 and E2 had remarkable in vitro inhibitory activities to Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc) with the EC50 values of 0.19 μg/ml and 0.21 μg/ml against Xoo, and 0.32 μg/ml and 0.41 μg/ml against Xoc, respectively, which were better than those of Zhongshengmycin (0.31 μg/ml and 0.73 μg/ml) and Bismerthiazol (77.48 μg/ml and 85.30 μg/ml). Polymyxins B1 and E2 had good protection and curative activities against rice bacterial leaf blight (BLB) and rice bacterial leaf streak (BLS) in vivo. The protection and curative activities of polymyxins B1 (45.8 and 35.8%, respectively) and E2 (41.2 and 37.0%, respectively) to BLB were superior to those of Zhongshengmycin (34.8 and 29.8%, respectively) and Bismerthiazol (38.0 and 33.5%, respectively). Meanwhile, the protection and curative activities of polymyxins B1 (44.8 and 39.8%, respectively) and E2 (42.9 and 39.9%, respectively) to BLS were also superior to those of Zhongshengmycin (39.7 and 32.0%, respectively) and Bismerthiazol (41.5 and 34.3%, respectively). Polymyxin B1 exerted the anti-pesticide properties via destroying the cell integrity of Xoo, reducing its infectivity and enhancing rice resistance against pathogens through activating the phenylpropanoid biosynthesis pathway of rice. It is indicated that polymyxin B1 and E2 were potential microbial pesticides for controlling rice bacterial disease.</p

Table_1_Polymyxin B1 and E2 From Paenibacillus polymyxa Y-1 for Controlling Rice Bacterial Disease.xlsx

To discover novel microbial pesticide for controlling rice bacterial disease, polymyxin B1 and E2 were firstly isolated from the supernatant of fermentation broth of Paenibacillus polymyxa Y-1 by bioactivity tracking separation. It is shown that polymyxin B1 and E2 had remarkable in vitro inhibitory activities to Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc) with the EC50 values of 0.19 μg/ml and 0.21 μg/ml against Xoo, and 0.32 μg/ml and 0.41 μg/ml against Xoc, respectively, which were better than those of Zhongshengmycin (0.31 μg/ml and 0.73 μg/ml) and Bismerthiazol (77.48 μg/ml and 85.30 μg/ml). Polymyxins B1 and E2 had good protection and curative activities against rice bacterial leaf blight (BLB) and rice bacterial leaf streak (BLS) in vivo. The protection and curative activities of polymyxins B1 (45.8 and 35.8%, respectively) and E2 (41.2 and 37.0%, respectively) to BLB were superior to those of Zhongshengmycin (34.8 and 29.8%, respectively) and Bismerthiazol (38.0 and 33.5%, respectively). Meanwhile, the protection and curative activities of polymyxins B1 (44.8 and 39.8%, respectively) and E2 (42.9 and 39.9%, respectively) to BLS were also superior to those of Zhongshengmycin (39.7 and 32.0%, respectively) and Bismerthiazol (41.5 and 34.3%, respectively). Polymyxin B1 exerted the anti-pesticide properties via destroying the cell integrity of Xoo, reducing its infectivity and enhancing rice resistance against pathogens through activating the phenylpropanoid biosynthesis pathway of rice. It is indicated that polymyxin B1 and E2 were potential microbial pesticides for controlling rice bacterial disease.</p

Discovery of Novel Pyrazole Derivatives with Improved Crop Safety as 4‑Hydroxyphenylpyruvate Dioxygenase-Targeted Herbicides

As one of the essential herbicide targets, 4-hydroxyphenylpyruvate dioxygenase (HPPD) has recently been typically used to produce potent new herbicides. In continuation with the previous work, several pyrazole derivatives comprising a benzoyl scaffold were designed and synthesized, and their inhibitory effects on Arabidopsis thaliana hydroxyphenylpyruvate dioxygenase (AtHPPD) and herbicidal activities were comprehensively evaluated in this study. Compound Z9 showed top-rank inhibitory activity to AtHPPD with an half-maximal inhibitory concentration (IC50) value of 0.05 μM, which was superior to topramezone (1.33 μM) and mesotrione (1.76 μM). Compound Z21 exhibited superior preemergence inhibitory activity against Echinochloa crusgalli, with stem and root inhibition rates of 44.3 and 69.6%, respectively, compared to topramezone (16.0 and 53.0%) and mesotrione (12.8 and 41.7%). Compounds Z5, Z15, Z20, and Z21 showed excellent postemergence herbicidal activities at a dosage of 150 g ai/ha, along with distinct bleaching symptoms and higher crop safety than topramezone and mesotrione, and they all were safe for maize, cotton, and wheat with injury rates of 0 or 10%. In addition, the molecular docking analysis also revealed that these compounds formed hydrophobic π–π interactions with Phe360 and Phe403 to AtHPPD. This study suggests that pyrazole derivatives containing a benzoyl scaffold could be used as new HPPD inhibitors to develop pre- and postemergence herbicides and be applied to additional crop fields

DataSheet2_Design, Synthesis, and Biological Activity of Novel Chalcone Derivatives Containing an 1,2,4-Oxadiazole Moiety.doc

To discover a lead compound for agricultural use, 34 novel chalcone derivatives containing an 1,2,4-oxadiazole moiety were designed and synthesized. Their nematocidal activities against Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Ditylenchus dipsaci and their antiviral activities against tobacco mosaic virus (TMV), pepper mild mottle virus (PMMoV), and tomato spotted wilt virus (TSWV) were evaluated. Biological assay results indicate that compounds A13 and A14 showed good nematocidal activities against B. xylophilus, A. besseyi, and D. dipsaci, with LC50 values of 35.5, 44.7, and 30.2 μg/ml and 31.8, 47.4, and 36.5 μg/ml, respectively, which are better than tioxazafen, fosthiazate, and abamectin. Furthermore, compound A16 demonstrated excellent protective activity against TMV, PMMoV, and TSWV, with EC50 values of 210.4, 156.2, and 178.2 μg/ml, respectively, which are superior to ningnanmycin (242.6, 218.4, and 180.5 μg/ml).</p

DataSheet1_Design, Synthesis, and Biological Activity of Novel Chalcone Derivatives Containing an 1,2,4-Oxadiazole Moiety.doc

To discover a lead compound for agricultural use, 34 novel chalcone derivatives containing an 1,2,4-oxadiazole moiety were designed and synthesized. Their nematocidal activities against Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Ditylenchus dipsaci and their antiviral activities against tobacco mosaic virus (TMV), pepper mild mottle virus (PMMoV), and tomato spotted wilt virus (TSWV) were evaluated. Biological assay results indicate that compounds A13 and A14 showed good nematocidal activities against B. xylophilus, A. besseyi, and D. dipsaci, with LC50 values of 35.5, 44.7, and 30.2 μg/ml and 31.8, 47.4, and 36.5 μg/ml, respectively, which are better than tioxazafen, fosthiazate, and abamectin. Furthermore, compound A16 demonstrated excellent protective activity against TMV, PMMoV, and TSWV, with EC50 values of 210.4, 156.2, and 178.2 μg/ml, respectively, which are superior to ningnanmycin (242.6, 218.4, and 180.5 μg/ml).</p

Novel Cyclized Derivatives of Ferulic Acid as Potential Antiviral Agents through Activation of Photosynthesis

To further develop new antiviral agents, several novel cyclized derivatives of ferulic acid were designed and synthesized. Their antiviral activities were evaluated against the cucumber mosaic virus (CMV), pepper mild mottle virus (PMMoV), and tomato spotted wilt virus (TSWV). The results showed that some ferulic acid derivatives exhibited desirable antiviral activities. Particularly, compound 5e exhibited excellent protective activities against CMV, PMMoV, and TSWV, with EC50 values of 167.2, 102.5, and 145.8 μg mL–1, respectively, which were superior to those obtained for trans-ferulic acid (581.7, 611.2, and 615.4 μg mL–1), dufulin (312.6, 302.5, and 298.2 μg mL–1), and ningnanmycin (264.3, 282.5, and 276.5 μg mL–1). Thereafter, the protective mechanisms of 5e were evaluated through photosynthesis evaluation, transcriptome profiling, and proteomic analysis. The results indicated that 5e significantly activated the expression levels of photosynthesis-related regulatory genes and proteins in tobacco plants and promoted the accumulation of defense molecules to resist viral infection. Thus, the findings of this study indicated that novel cyclized ferulic acid derivatives are potential antiviral agents that act via regulating photosynthesis in the host

Design, synthesis and nematocidal activity of novel 1,2,4-oxadiazole derivatives with a 1,3,4-thiadiazole amide moiety

A series of novel 1,2,4-oxadiazole derivatives containing 1,3,4-thiadiazole amide group was synthesized and their nematocidal activities were evaluated. The results indicated that compounds 4-methoxy-N-(5-(((3-(p-tolyl)-1,2,4-oxadiazol-5-yl)methyl)thio)-1,3,4-thiadiazol-2-yl)benzamide 4i and N-(5-(((3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)methyl)thio)-1,3,4-thiadiazol-2-yl)benzamilde 4p showed good nematocidal activity against Bursaphelenchus xylophilus. The corrected mortality of compounds 4i and 4p at 200 mg/L was 57.1% and 60.1%, respectively, which are much better than 13.5% of the commercial seed coating agent Tioxazafen. Compounds 4i and 4p dramatically decreased the head swinging, body fluctuation, and body bending frequency of B. xylophilus after 12 h of treatment. Moreover, they inhibited the respiration, decreased the oxygen consumption, and caused fluid leakage of B. xylophilus. In addition, compounds 4i and 4p have good druggability properties similar to those of Tioxazafen. The present work indicates that compounds 4i or 4p could be promising lead compounds for further development of nematicides.</p