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.

Half of the world's population depends on rice for their calories. Protecting rice in the growth period from damage caused by phytopathogens is faced with a great challenge under the frequent extreme climate. To find novel fungicides to control rice diseases, 35 novel phenylthiazole‐1,3,4‐oxadiazole‐thioether (sulfone) derivatives were synthesized and evaluated for their efficacy against destructive fungal and bacterial diseases of rice. Bioassay results demonstrated that most of G‐series compounds possessed excellent antifungal and antibacterial activities. In particular, compounds G1 (EC₅₀ = 2.22 μg/mL, R.s) and G7 (EC₅₀ = 2.76 μg/mL, R.s) showed the most promising antifungal activities in vitro and exhibited superior protective and curative activities against rice sheath blight in vivo compared with commercial carbendazim. Surprisingly, compound G2 exhibited the remarkable antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo) with an EC₅₀ value of 1.98 μg/mL, and demonstrated superior protective activity (88.08%) than thiodiazole copper (79.39%) against rice bacterial leaf blight at 200 μg/mL. The abovementioned results fully manifested that the phenylthiazole‐1,3,4‐oxadiazole‐sulfone structure, especially compounds G1 and G2, had the potential to develop as commercial agents for controlling rice fungal and bacterial diseases.

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.