Design, synthesis and antifungal activity of novel amide derivatives containing a pyrrolidine moiety as potential succinate dehydrogenase inhibitors.

To discover new succinate dehydrogenase inhibitors (SDHI) fungicides, a series of amide derivatives containing a pyrrolidine moiety were designed and synthesized, and their antifungal activities were evaluated against Monilinia fructicola (M. fructicola), Rhizoctonia solani (R. solani), Fusarium graminearum schw (F. graminearum), Fusarium oxysporum (F. oxysporum), and Phytophthora infestans (P. infestans). Some compounds showed excellent antifungal activities against the five fungi. Among them, compound 6 showed broad-spectrum inhibitory activities. The EC50 of compound 6 against M. fructicola, R. solani, F. graminearum, F. oxysporum, and P. infestans were 2.13, 14.42, 1.69, 27.79, and 27.12 mg/L, respectively. In addition, compound 6 can effectively inhibit the spore germination of M. fructicola and has moderate damage to the cell membrane. Compound 6 can effectively inhibit succinate dehydrogenase (SDH) of M. fructicola, and can significantly increase the expression levels of SDHC and SDHD. Compound 6 can be used as a lead structure for developing new SDH inhibitors.

Novel amide derivatives containing an imidazo[1,2-a]pyridine moiety: Design, synthesis as potential nematicidal and antibacterial agents.

To discover new nematicides, a series of novel amide derivatives containing an imidazo[1,2-a]pyridine moeity were designed and synthesized. Among the title compounds, compounds 3 and 27 exhibited good nematicidal activities against Aphelenchoides besseyi (rice white-tip nematode), with LC50 values against of 27.3 and 35.9 mg/L, respectively, which were superior to that of fosthiazate (45.4 mg/L). Meanwhile, the LC50 value of compound 27 against Caenorhabditis elegans was 5.7 mg/L, which was superior to that of fosthiazate (77.2 mg/L). Compound 27 not only binds well to acetylcholinesterase (AChE) of nematodes, but also has a good inhibitory activity against AChE. Thus, AChE may be a potential target of compound 27 against nematodes. Unexpectedly, compound 28 exhibited excellent antibacterial activities with EC50 values of 1.2 and 3.1 mg/L against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), respectively, which were superior to those of bismerthiazol (68.6 and 77.1 mg/L) and thiodiazole copper (80.8 and 96.6 mg/L). The curative and protective activities of compound 28 against bacterial leaf blight were 37.0% and 36.8% at 50 mg/L, respectively, which were higher than those of thiodiazole copper (16.1% and 15.5%). In addition, compound 28 may inhibit the growth of Xoo by affecting the production of cell membranes and extracellular polysaccharides. Amide derivatives containing an imidazo[1,2-a]pyridine moeity can be used as good lead-structures to discover new nematicidal and antibacterial agents in the future.

Pyrido [1,2-a] Pyrimidinone Mesoionic Compounds Containing Vanillin Moiety: Design, Synthesis, Antibacterial Activity, and Mechanism.

Xanthomonas oryzae pv. oryzicola (Xoo) is a plant pathogen responsible for rice bacterial blight disease that remains challenging for prevention and cure. To discover innovative and extremely potent antibacterial agents, vanillin moiety was introduced to develop a series of novel mesoionic derivatives. Compound 15 demonstrated excellent in vitro antibacterial activity against Xoo, with a 50% effective concentration value (EC50) of 27.5 µg/mL, which was superior to that of the positive control agent thiodiazole copper (97.1 µg/mL) and comparable to that of compound "A11" (17.4 µg/mL). The greenhouse pot experiment also revealed that compound 15 had 38.5% curative and 36.8% protective efficacy against rice bacterial leaf blight in vivo at 100 µg/mL, which was higher than those of thiodiazole copper (31.2 and 32.6%, respectively) and compound "A11" (29.6 and 33.2%, respectively). Compound 15 enhanced the activities of related defense enzymes, increased chlorophyll content, and promoted the resistance of rice to bacterial infection by modulating the photosynthetic pathway. This study provides a basis for the subsequent structural modification and mechanism research of mesoionic derivatives.

Recent Research Progress: Discovery of Anti-Plant Virus Agents Based on Natural Scaffold.

Plant virus diseases, also known as "plant cancers", cause serious harm to the agriculture of the world and huge economic losses every year. Antiviral agents are one of the most effective ways to control plant virus diseases. Ningnanmycin is currently the most successful anti-plant virus agent, but its field control effect is not ideal due to its instability. In recent years, great progress has been made in the research and development of antiviral agents, the mainstream research direction is to obtain antiviral agents or lead compounds based on structural modification of natural products. However, no antiviral agent has been able to completely inhibit plant viruses. Therefore, the development of highly effective antiviral agents still faces enormous challenges. Therefore, we reviewed the recent research progress of anti-plant virus agents based on natural products in the past decade, and discussed their structure-activity relationship (SAR) and mechanism of action. It is hoped that this review can provide new inspiration for the discovery and mechanism of action of novel antiviral agents.

Evaluation of Scopoletin from Penicillium janthinellum Snef1650 for the Control of Heterodera glycines in Soybean.

Soybean cyst nematode (SCN) (Heterodera glycines Ichinohe) is responsible for causing a major soybean disease globally. The fungal strain Penicillium janthinellum Snef1650 was evaluated against H. glycines. However, the effective determinants of the P. janthinellum strain are unknown. By performing pot experiments, a functioning compound was isolated from P. janthinellum Snef1650 through organic solvent extraction, semi-preparative HPLC, Sephadex LH-20 column chromatography, and silica gel column chromatography, and the isolated compound was identified to be scopoletin through 1H NMR, 13C NMR, and HPLC-MS. The pot experiments indicated that the treatment of soybean seeds with scopoletin drastically reduced the SCN population. The field experiments performed in 2017 and 2018 revealed that scopoletin decreased over 43.7% juveniles in the roots and over 61.55% cysts in the soil. Scopoletin treatment also promoted soybean growth and improved its yield, with an increase in plot yield by >5.33%. Scopoletin obtained from P. janthinellum Snef1650 could be used as an anti-H. glycines biocontrol agent.

Isolation and identification of induced systemic resistance determinants from Bacillus simplex Sneb545 against Heterodera glycines.

Heterodera glycines is one of the most destructive pathogens of soybean. Soybean seeds coated with Bacillus simplex Sneb545 have shown resistance to H. glycines as a result of induced systemic resistance (ISR) in the plants. In this study, we aimed to identify the resistance-inducing determinants from this B. simplex strain. Combining the ISR bioassay, six ISR-active compounds were isolated from a culture of B. simplex Sneb545 using organic solvent gradient extraction, silica gel column chromatography, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography (HPLC), and all systems were based on activity tracking. The compounds were determined as cyclic(Pro-Tyr), cyclic(Val-Pro), cyclic(Leu-Pro), uracil, phenylalanine, and tryptophan using 1H NMR and 13C NMR. In plants from seeds coated with Bacillus simplex Sneb545, these six ISR-active compounds delayed the development of H. glycines in soybean roots. Moreover, cyclic(Pro-Tyr), cyclic(Val-Pro), and tryptophan reduced the number of nematodes in soybean roots. The expression levels of defense-related genes with cyclic(Val-Pro), tryptophan and uracil treatment soybean analysed using Quantitative real-time PCR (qRT-PCR). The results indicate cyclic(Val-Pro), tryptophan and uracil induced the expression of defense-related genes involved in the SA- and JA-pathways to against H. glycines. Our research results provide new agents for the control of H. glycines.