Design, Synthesis and Bioassay of 2-Phenylglycine Derivatives as Potential Pesticide Candidates.

Plant diseases can seriously affect the growth of food crops and economic crops. To date, pesticides are still among the most effective methods to prevent and control plant diseases worldwide. Consequently, to develop potential pesticide molecules, a series of novel 2-phenylglycine derivatives containing 1,3,4-oxadiazole-2-thioethers were designed and synthesized. The bioassay results revealed that G19 exhibited great in vitro antifungal activity against Thanatephorus cucumeris with an EC50 value of 32.4 µg/mL, and in vivo antifungal activity against T. cucumeris on rice leaves at a concentration of 200.0 µg/mL (66.9 %) which was close that of azoxystrobin (73.2 %). Compounds G24 (80.2 %), G25 (89.4 %), and G27 (83.3 %) exhibited impressive in vivo inactivation activity against tobacco mosaic virus (TMV) at a concentration of 500.0 µg/mL, which was comparable to that of ningnanmycin (96.3 %) and markedly higher than that of ribavirin (55.6 %). The antibacterial activity of G16 (63.1 %), G26 (89.9 %), G27 (78.0 %), and G28 (68.0 %) against Xoo at a concentration of 50.0 µg/mL was higher than that of thiadiazole copper (18.0 %) and bismerthiazol (38.9 %). Preliminary mechanism studies on the antifungal activity against T. cucumeris demonstrated that G19 can affect the growth of mycelia by disrupting the integrity of the cell membrane and altering the permeability of the cell. These studies revealed that the amino acid derivatives containing a 1,3,4-oxadiazole moiety exhibited certain antifungal, antibacterial, and anti-TMV activities, and these derivatives can be further modified and developed as potential pesticide molecules.

Novel 1,3,4-Thiadiazole Derivatives: Synthesis, Antiviral Bioassay and Regulation the Photosynthetic Pathway of Tobacco against TMV Infection.

Tobacco mosaic virus (TMV) is a systemic virus that poses a serious threat to crops worldwide. In the present study, a series of novel 1-phenyl-4-(1,3,4-thiadiazole-5-thioether)-1H-pyrazole-5-amine derivatives was designed and synthesized. In vivo antiviral bioassay results indicated that some of these compounds exhibited excellent protective activity against TMV. Among the compounds, E2 (EC50 = 203.5 µg/mL) was superior to the commercial agent ningnanmycin (EC50 = 261.4 µg/mL). Observation of tobacco leaves infected with TMV-GFP revealed that E2 could effectively inhibit the spread of TMV in the host. Further plant tissue morphological observation indicated that E2 could induce the tight arrangement and alignment of the spongy mesophyll and palisade cells while causing stomatal closure to form a defensive barrier to prevent viral infection in the leaves. In addition, the chlorophyll content of tobacco leaves was significantly increased after treatment with E2, and the net photosynthesis (Pn) value was also increased, which demonstrated that the active compound could improve the photosynthetic efficiency of TMV-infected tobacco leaves by maintaining stable chlorophyll content in the leaves, thereby protecting host plants from viral infection. The results of MDA and H2O2 content determination revealed that E2 could effectively reduce the content of peroxides in the infected plants, reducing the damage to the plants caused by oxidation. This work provides an important support for the research and development of antiviral agents in crop protection.

Study of the in vivo antiviral activity against TMV treated with novel 1-(t-butyl)-5-amino-4-pyrazole derivatives containing a 1,3,4-oxadiazole sulfide moiety.

A series of new 1-tert-butyl-5-amino-4-pyrazole bioxadiazole sulfide derivatives containing a 1,3,4-oxadiazole moiety were designed and synthesized. The bioactivity results showed that some title compounds exhibited excellent protective activity against TMV and certain insecticidal activity. Among the tested compounds, the EC50 values of 5d, 5j, 5k and 5l were 165.8, 163.2, 159.7 and 193.1 mg/L, respectively, which are better than the EC50 value of ningnanmycin (271.3 mg/L). The chlorophyll contents and the defense enzyme activities of the tobacco leaves after treatment with 5j were significantly increased, which indicated that this series of title compounds may induce the systemic acquired resistance of host to defend against diseases. Further in vivo protective activity research on 5j using TMV with a GFP gene tag found that it can effectively inhibit the spread of TMV in inoculated tobacco. A morphological study with TEM revealed that title compound 5h can cause a distinct break of the rod-shaped TMV. Moreover, the insecticidal activity revealed that the fatality rates of 5a, 5b and 5m against aphidoidea were 85%, 83% and 87%, respectively, which indicated that the title compounds can effectively block the common carrier of plant viruses, thereby effectively reducing the TMV infection risk of tobacco. This series of synergistic effects provide key information for the research and development of antiviral agents.

Design, Synthesis, and Study of the Dual Action Mode of Novel N-Thienyl-1,5-disubstituted-4-pyrazole Carboxamides against Nigrospora oryzae.

Due to the single target but extensive application of commercialized succinate dehydrogenase inhibitors (SDHIs), resistance problems have gradually become apparent in recent years. To solve this problem, a series of novel N-thienyl-1,5-disubstituted-1H-4-pyrazole carboxamide derivatives were designed and synthesized in this work based on the active skeleton 5-trifluoromethyl-4-pyrazole carboxamide. The bioassay results indicated that some target compounds exhibited excellent in vitro antifungal activities against the eight phytopathogenic fungi tested. Among them, the EC50 values of T4, T6, and T9 against Nigrospora oryzae were 5.8, 1.9, and 5.5 mg/L, respectively. The in vivo protective and curative activities of 40 mg/L T6 against rice infected with N. oryzae were 81.5% and 43.0%, respectively. Further studies revealed that T6 not only significantly inhibited the growth of N. oryzae mycelia but also effectively hindered spore germination and germ tube elongation. Morphological studies using scanning electron microscopy (SEM), fluorescence microscopy (FM), and transmission electron microscopy (TEM) found that T6 could affect the mycelium membrane integrity by increasing cell membrane permeability and causing peroxidation of cellular lipids, and these results were further verified by measuring the malondialdehyde (MDA) content. The IC50 value of T6 against succinate dehydrogenase (SDH) was 7.2 mg/L, lower than that of the commercialized SDHI penthiopyrad (3.4 mg/L). Further, ATP content detection and the results after docking T6 and penthiopyrad suggested that T6 was a potential SDHI. These studies demonstrated that active compound T6 could both inhibit the activity of SDH and affect the integrity of the cell membrane at the same time via a dual action mode, which is different from the mode of action of penthiopyrad. Thus, this study provides a new idea for a strategy to delay resistance and diversify the structures of SDHIs.