To effectively control the infection of plant pathogens, we designed and synthesized a series of phenylthiazole derivatives containing a 1,3,4-thiadiazole thione moiety and screened for their antibacterial potencies against Ralstonia solanacearum, Xanthomonas oryzae pv. oryzae, as well as their antifungal potencies against Sclerotinia sclerotiorum, Rhizoctonia solani, Magnaporthe oryzae and Colletotrichum gloeosporioides. The chemical structures of the target compounds were characterized by ¹H NMR, ¹³C NMR and HRMS. The bioassay results revealed that all the tested compounds exhibited moderate-to-excellent antibacterial and antifungal activities against six plant pathogens. Especially, compound 5k possessed the most remarkable antibacterial activity against R. solanacearum (EC₅₀ = 2.23 μg/mL), which was significantly superior to that of compound E1 (EC₅₀ = 69.87 μg/mL) and the commercial agent Thiodiazole copper (EC₅₀ = 52.01 μg/mL). Meanwhile, compound 5b displayed the most excellent antifungal activity against S. sclerotiorum (EC₅₀ = 0.51 μg/mL), which was equivalent to that of the commercial fungicide Carbendazim (EC₅₀ = 0.57 μg/mL). The preliminary structure-activity relationship (SAR) results suggested that introducing an electron-withdrawing group at the meta-position and ortho-position of the benzene ring could endow the final structure with remarkable antibacterial and antifungal activity, respectively. The current results indicated that these compounds were capable of serving as promising lead compounds.

Crop fungal diseases pose a serious threat to global crop production and quality. Developing new and efficient fungicides is an important measure to control crop diseases. Phenylthiazole was found to be an excellent antifungal skeleton based on our previous study on the structural optimization and biological activity of the natural product thiasporine A. To find new fungicides, 45 phenylthiazole derivatives containing an acylhydrazone moiety were designed and synthesized by the principle of active substructure splicing. Forty-two of the forty-five compounds are novel, except for compounds E1, E14, and E33. Their structures were structurally characterized by ¹H NMR, ¹³C NMR, and HRMS. The antifungal activities of the target compounds against Magnaporthe oryzae Colletotrichum camelliaet, Bipolaris maydis, and Sclerotinia sclerotiorum were evaluated at 25 μg/mL. The bioassay results revealed that most of these compounds exhibited excellent antifungal activities against M. oryzae and C. camelliaet at 25 μg/mL. In particular, compounds E4, E10, E14, E17, E23, E26, and E27 showed the inhibition rate of more than 80% against M. oryzae, with EC₅₀ values of 1.66, 2.01, 2.26, 1.45, 1.50, 1.29, and 2.65 μg/mL, respectively, which were superior to that of the commercial fungicides Isoprothiolane (EC₅₀ = 3.22 μg/mL) and Phenazine-1-carboxylic acid (EC₅₀ = 27.87 μg/mL). The preliminary structure–activity relationship (SAR) results suggested that introducing methyl, halogen, or methoxy at the ortho-position of R¹ and the para-position of R² can endow the final structure with excellent antifungal activity against M. oryzae. The current results provide useful data for developing phenylthiazole derivatives as new fungicides for controlling rice blast caused by M. oryzae.

The natural pesticide phenazine-1-carboxylic acid (PCA) is known to lack phloem mobility, whereas Metalaxyl is a representative phloem systemic fungicide. In order to endow PCA with phloem mobility and also enhance its antifungal activity, thirty-two phenazine-1-carboxylic acid-N-phenylalanine esters conjugates were designed and synthesized by conjugating PCA with the active structure N-acylalanine methyl ester of Metalaxyl. All target compounds were characterized by ¹H NMR, ¹³C NMR and HRMS. The antifungal evaluation results revealed that several target compounds exhibited moderate to potent antifungal activities against Sclerotinia sclerotiorum, Bipolaris sorokiniana, Phytophthora parasitica, Phytophthora citrophthora. In particular, compound F7 displayed excellent antifungal activity against S. sclerotiorum with an EC₅₀ value of 6.57 µg/mL, which was superior to that of Metalaxyl. Phloem mobility study in castor bean system indicated good phloem mobility for the target compounds F1–F16. Particularly, compound F2 exhibited excellent phloem mobility; the content of compound F2 in the phloem sap of castor bean was 19.12 μmol/L, which was six times higher than Metalaxyl (3.56 μmol/L). The phloem mobility tests under different pH culture solutions verified the phloem translocation of compounds related to the “ion trap” effect. The distribution of the compound F2 in tobacco plants further suggested its ambimobility in the phloem, exhibiting directional accumulation towards the apical growth point and the root. These results provide valuable insights for developing phloem mobility fungicides mediated by exogenous compounds.

In the search for crop protectants, amino acid ester conjugates have been widely investigated as potential antifungal agents. In this study, a series of rhein–amino acid ester conjugates were designed and synthesized in good yields, and their structures were confirmed by ¹H-NMR, ¹³C-NMR and HRMS. The bioassay results revealed that most of the conjugates exhibited potent inhibitory activity against R. solani and S. sclerotiorum. In particular, conjugate 3c had the highest antifungal activity against R. solani with an EC₅₀ value of 0.125 mM. For S. sclerotiorum, conjugate 3m showed the highest antifungal activity with an EC₅₀ value of 0.114 mM. Satisfactorily, conjugate 3c exhibited better protective effects than that of the positive control, physcion, against powdery mildew in wheat. This research supports the role of rhein–amino acid ester conjugates as potential antifungal agents for plant fungal diseases.

With the long-term use of certain types of traditional chemical fungicides, phytopathogen resistance and environmental pollution have made the application of these fungicides face unprecedented challenges. Therefore, using the low toxicity and structural diversity of natural product analogs to develop alternatives has become an important tactic to improve control efficiency and reduce pathogen resistance, as well as environmental risks. In this study, thirty-eight rhein derivatives were synthesized after our continuous efforts aiming to discover new anthraquinone-based antifungal agents. Their structures were characterized by ¹H-NMR, ¹³C-NMR and high-resolution mass spectrometry. The antifungal activities of rhein derivatives were first evaluated against four phytopathogenic fungi. The bioassay results indicated that most derivatives exhibited good antifungal activity against Rhizoctonia solani at 0.5 mM in vitro. Compounds 3e, 3j, 4a, 9d and 10f showed potent activities against R. solani, with inhibition rates over 50% at a low concentration of 0.2 mM in vitro. In particular, compound 10a strongly inhibited the growth of Sclerotinia sclerotiorum, Fusarium graminearum and P. capsica, with EC₅₀ values of 0.079 mM, 0.082 mM and 0.134 mM, respectively, which are comparable to the commercial biofungicide phenazine-1-carboxylic acid (PCA). An in vivo study showed that 10a presented excellent curative and protective activities (92.1% and 91.1%, 0.2 mM) against wheat powdery mildew. The phytotoxicity results indicated that rhein amino acid derivatives could significantly eliminate phytotoxicity to rice and rape and could be safely used in these two crops. The resistance development assay indicated that these rhein derivatives could effectively avoid the risk of resistance development in these two strains of fungi, R. solani and S. sclerotiorum. In conclusion, rhein derivatives can be used for the development of potential agricultural fungicides.

The phloem mobility of fungicides is a highly advantageous property for controlling plant root and vascular diseases. In order to develop phloem-mobile fungicides with enhanced antifungal activity, a new pesticide vectorization strategy was proposed for using exogenous compounds as vector groups in this study. Nine novel PCA amide derivatives containing heterocyclic carboxylic acids were designed and synthesized by coupling PCA with a heterocyclic carboxylic acid via an amide linkage. In vitro bioassays revealed that nine target compounds exhibited moderate to strong antifungal activity against the tested fungal pathogens. Notably, compound D4 demonstrated superior inhibitory effects against multiple pathogenic fungi. The results of phloem mobility tests demonstrated that five target compounds, D1, D2, D4, D7, and D9, exhibited phloem mobility, which is consistent with possible carrier-mediated transport. In pot experiments, compound D4 exhibited significantly better protective and curative efficacy against rice sheath blight than PCA, a benefit that may stem from its phloem mobility. Further systemic translocation studies in tobacco (Nicotiana tabacum L.) confirmed that compound D4 is readily absorbed by leaves and efficiently distributed throughout the plant, with pronounced accumulation in roots and stems. This translocation pattern may play a significant role in improving the effectiveness of compound D4 in controlling root and vascular diseases.