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.

We prepared 16 novel hydroxybenzoic acid ester conjugates of phenazine-1-carboxylic acid (PCA) and investigated their biological activity. Most of the synthesized conjugates displayed some level of fungicidal activities in vitro against five phytopathogenic fungi. Nine conjugates 5b, 5c, 5d, 5e, 5h, 5i, 5m, 5n and 5o (EC50 between 3.2 μg/mL and 14.1 μg/mL) were more active than PCA (EC50 18.6 μg/mL) against Rhizoctonia solani. Especially conjugate 5c showed the higher fungicidal activity against Rhizoctonia solani which is 6.5-fold than PCA. And the results of the bioassay indicated that the fungicidal activity of conjugates was associated with their LogP, and the optimal LogP values of the more potent fungicidal activities within these conjugates ranged from 4.42 to 5.08. The systemic acquired resistance induced by PCA–SA ester conjugate 5c against rice sheath blight disease in rice seedlings was evaluated. The results revealed that PCA–SA ester conjugate 5c retained the resistance induction activity of SA against rice sheath blight.

Developing fungicides with phloem mobility that can be applied to leaves to control root or vascular pathogens has long been desirable. To achieve this goal, an efficient and economical strategy involves introducing an amino acid into the existing highly active parent pesticide molecule. Hence, 12 L-phenazine-1-carboxylic acid (PCA)-amino acid conjugates 4a–l were designed and synthesized via a simple synthetic route. In vitro bioassays results showed that all synthesized compounds 4a–l exhibited certain fungicidal activities against six tested fungi. Compound 4c exhibited relatively good fungicidal activity against Rhizoctonia solani, and the EC₅₀ value was 0.084 ± 0.006 mmol/L. The phloem mobility experiments revealed that introducing an amino acid to PCA could effectively endow PCA with phloem mobility in R. communis L. Among them, nine conjugates were found in phloem sap, and L-PCA-Valine 4d exhibited the highest phloem mobility. Analysis results from the prediction of the Kleier model indicated that an active carrier-mediated mechanism may be involved in L-PCA-amino acid conjugates—a result that needs to be confirmed and complemented with further tests. The current research provides useful data for modifying non-phloem-mobile fungicidal molecules to phloem-mobile types.

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.

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.

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.