Antifungal Activity of Novel Indole Derivatives Containing 1,3,4-Thiadiazole.

In this study, 24 indole derivatives containing 1,3,4-thiadiazole were discovered and synthesized. The target compounds' antifungal efficacy against 14 plant pathogenic fungal pathogens was then determined in vitro. With an EC50 value of 2.7 µg/mL, Z2 demonstrated the highest level of bioactivity among them against Botrytis cinerea (B.c.), exceeding the concentrations of the control prescription drugs azoxystrobin (Az) (EC50 = 14.5 µg/mL) and fluopyram (Fl) (EC50 = 10.1 µg/mL). Z2 underwent in vivo testing on blueberry leaves in order to evaluate its usefulness in real-world settings. A reasonable protective effect was obtained with a control effectiveness of 93.0% at 200 µg/mL, which was superior to those of Az (83.0%) and Fl (52.0%). At 200 µg/mL, this chemical had an efficacy of 84.0% in terms of curative efficacy. These figures outperformed those of Az (69.0%) and Fl (48.0%). Scanning electron microscopy (SEM) experiments and light microscopy experiments showed that Z2 altered the integrity of the cell wall and cell membrane of the pathogenic fungus B.c., which led to an increase in the content of malondialdehyde (MDA), cellular leakage, and cellular permeability. Enzyme activity assays and molecular docking studies indicated that Z2 could act as a potential succinate dehydrogenase inhibitor (SDHI). It was hypothesized that Z2 could cause disruption of mycelial cell membranes, which in turn leads to mycelial death. According to the research, indole derivatives containing 1,3,4-thiadiazole were expected to evolve into new fungicides due to their significant antifungal effects on plant fungi.

Antiviral activity evaluation and action mechanism of chalcone derivatives containing phenoxypyridine.

In this paper, a series of phenoxypyridine-containing chalcone derivatives (L1-L28) were designed and synthesized, characterized on NMR and HRMS. Ningnanmycin (NNM) was used as a control agent. The results of the antiviral activity testing showed that the curative activity EC50 values of L1 and L4 against TMV were 140.5 and 90.7 µg/mL, respectively, which were superior to that of NNM (148.3 µg/mL). The EC50 values of 154.1, 102.6 and 140.0 µg/mL for the anti-TMV protective activities of L1, L4 and L15 were superior to that of NNM (188.2 µg/mL). The mechanism of action between L4 and NNM and tobacco mosaic virus capsid protein (TMV-CP) was preliminarily investigated. The results of microscale thermophoresis (MST) experiments showed that L4 had a strong binding affinity for TMV-CP with a dissociation constant Kd value of 0.00149 µM, which was better than that of NNM (2.73016 µM). The results of molecular docking experiments showed that L4 formed shorter hydrogen bonds with amino acid residues of TMV-CP than NNM and formed more amino acid residues than NNM, which indicated that L4 was more tightly bound to TMV-CP. This study suggested that phenoxypyridine-containing chalcone derivatives can be used as new anti-TMV drugs through further research and development.

Antiviral activity evaluation and action mechanism of myricetin derivatives containing thioether quinoline moiety.

A variety of myricetin derivatives containing thioether quinoline moiety were designed and synthesized. Their structures of title compounds were determined by 1H NMR, 13C NMR, 19F NMR, and HRMS. Single-crystal X-ray diffraction experiments were carried out with B4. Antiviral activity indicated that some of the target compounds exhibited remarkable anti-tobacco mosaic virus (TMV) activity. In particular, compound B6 possessed significant activity. The half maximal effective concentration (EC50) value of the curative activity of compound B6 was 169.0 µg/mL, which was superior to the control agent ningnanmycin (227.2 µg/mL). Meanwhile, the EC50 value of the protective activity of compound B6 was 86.5 µg/mL, which was better than ningnanmycin (179.2 µg/mL). Microscale thermophoresis (MST) indicated that compound B6 had a strong binding capability to the tobacco mosaic virus coat protein (TMV-CP) with a dissociation constant (Kd) value of 0.013 µmol/L, which was superior to that of myricitrin (61.447 µmol/L) and ningnanmycin (3.215 µmol/L). And the molecular docking studies were consistent with the experimental results. Therefore, these novel myricetin derivatives containing thioether quinoline moiety could become potential alternative templates for novel antiviral agents.

Design, synthesis and bioactivity of myricetin derivatives for control of fungal disease and tobacco mosaic virus disease.

A series of myricetin derivatives containing isoxazole were designed and synthesized. All the synthesized compounds were characterized by NMR and HRMS. In terms of antifungal activity, Y3 had a good inhibitory effect on Sclerotinia sclerotiorum (Ss), and the median effective concentration (EC50) value was 13.24 µg mL-1, which was better than azoxystrobin (23.04 µg mL-1) and kresoxim-methyl (46.35 µg mL-1). Release of cellular contents and cell membrane permeability experiments further revealed that Y3 causes the destruction of the cell membrane of the hyphae, which in turn plays an inhibitory role. The anti-tobacco mosaic virus (TMV) activity in vivo showed that Y18 had the best curative and protective activities, with EC50 values of 286.6 and 210.1 µg mL-1 respectively, the effect was better than ningnanmycin. Microscale thermophoresis (MST) data showed that Y18 had a strong binding affinity with tobacco mosaic virus coat protein (TMV-CP), with a dissociation constant (K d) value of 0.855 µM, which was better than ningnanmycin (2.244 µM). Further molecular docking revealed that Y18 interacts with multiple key amino acid residues of TMV-CP, which may hinder the self-assembly of TMV particles. Overall, after the introduction of isoxazole on the structure of myricetin, its anti-Ss and anti-TMV activities have been significantly improved, which can be further studied.

Design, Synthesis, Biological Activity Evaluation and Action Mechanism of Myricetin Derivatives Containing Thiazolebisamide.

The plant diseases caused by a variety of pathogens such as viruses, bacteria and fungi pose a great threat to global food production and food safety. Therefore, the search for green, efficient and pollution-free pesticides has become an important task. In this article, 23 myricetin derivatives containing thiazolebisamides active groups have been designed and synthesized. Their activities were evaluated by performing in vitro antibacterial and in vivo antiviral assays, microscale thermophoresis (MST) and molecular docking assays. The results of in vivo antiviral assays showed that compounds A4 and A23 exhibited good antiviral activity with EC50 values of 79.0 and 54.1 µg/mL for therapeutic activity and 103.3 and 91.2 µg/mL for protective activity, respectively. The dissociation constants (Kd) values of compounds A4 and A23 against TMV-CP were 0.021 and 0.018 µM, respectively, determined by microscale thermophoresis (MST), which were much smaller than those of the commercial drug ningnanmycin (NNM), which were 2.84 µM. The interaction of compounds A4, A23 with TMV-CP was further verified at the molecular level. In addition, in vitro antifungal assays of this series of compounds showed that they exhibited some inhibitory activity against a variety of fungi, especially against the phytophthora capsici. Among them, A13 and A20 showed similar inhibitory activity to the control drug azoxystrobin at 100 µg/mL against the phytophthora capsici.