Novel Sulfoximine Derivatives Containing Cyanoguanidine and Nitroguanidine Moieties: Design, Synthesis, and Bioactivities.

A total of 32 novel sulfoximines bearing cyanoguanidine and nitroguanidine moieties were designed and synthesized by a rational molecule design strategy. The bioactivities of the title compounds were evaluated and the results revealed that some of the target compounds possessed excellent antifungal activities against six agricultural fungi, including Sclerotinia sclerotiorum, Fusarium graminearum, Phytophthora capsici, Botrytis cinerea, Rhizoctonia solani, and Pyricularia grisea. Among them, compounds 8e1 and 8e4 exhibited significant efficacy against P. grisea with EC50 values of 2.72 and 2.98 µg/mL, respectively, which were much higher than that of commercial fungicides boscalid (47.95 µg/mL). Interestingly, in vivo assays determined compound 8e1 possessed outstanding activity against S. sclerotiorum with protective and curative effectiveness of 98 and 95.6% at 50 µg/mL, which were comparable to those of boscalid (93.2, 91.9%). The further preliminary mechanism investigation disclosed that compound 8e1 could damage the structure of the cell membrane of S. sclerotiorum, increase its permeability, and suppress its growth. Overall, the findings enhanced that these novel sulfoximine derivatives could be potential lead compounds for the development of new fungicides.

Design, synthesis, and antifungal activities of novel sulfoximine derivatives for plant protection.

BACKGROUND: Fungicides play a significant role in the integrated management of plant pathogens. However, the irrational application of fungicides with similar structures has led to development of cross-resistance, therefore there is a need to seek novel fungicides with new structures. RESULTS: Twenty-eight novel sulfoximine derivatives incorporating nitroguanidine moieties were designed, synthesized, and evaluated as antifungal agents. The bioassay results indicated that most of the synthesized compounds displayed excellent fungicidal activities against Sclerotinia sclerotiorum, Rhizoctonia solani, Fusarium graminearum, and Pyricularia grisea. Among these, compounds 6c4 , 6c5 , and 6c6 exhibited remarkable fungicidal activities against P. grisea, with EC50 values of 1.28, 1.17, and 1.68 µg mL-1 , respectively. In addition, compound 6c2 displayed the most potent activity against S. sclerotiorum (EC50  = 3.64 µg mL-1 ). Further in vivo fungicidal activity screening against S. sclerotiorum demonstrated that the protective and curative effects of compound 6c2 were 98.1% and 91.3% at 25 µg mL-1 , respectively, comparable to that of boscalid (94.4%, 89.6%). The preliminary mechanism study found that the hyphae of S. sclerotiorum treated with compound 6c2 was abnormal with mycelial collapse and membrane permeability increase. The present findings can help to develop new fungicides for crop protection. CONCLUSION: Novel sulfoximine derivatives containing nitroguanidine possess potential antifungal activity, and the unique structure may offer an alternative option for fungicide development in the future. © 2022 Society of Chemical Industry.

Design, Synthesis, and Antifungal Activity of Sulfoximine Derivatives Containing Nitroguanidine Moieties.

To discover novel pesticide candidates, a series of sulfoximine derivatives were designed and synthesized via the oxidation coupling reaction of sulfides and N-alkyl nitroguanidines. The compounds were evaluated for their antifungal activity against six phytopathogenic fungi. Most of them exhibited a broad spectrum of fungicidal activity in vitro. Compound 8IV-b displayed good fungicidal activity against Sclerotinia sclerotiorum, Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, and Phytophthora capsici, with EC50 value of 12.82, 12.50, 17.25, 31.08, and 30.11 mg/L, respectively. In addition, compounds 8III-c and 8IV-e had EC50 values of 22.23 and 20.67 mg/L against P. capsic, which were significantly better than that of the commercial procymidone (118.15 mg/L). Strikingly, 8IV-d exhibited satisfactory fungicidal activity against B. cinerea, which was comparable to control procymidone in terms of their EC50 values (7.42 versus 10.83 mg/L), and the bioassays in vivo further confirmed that 8IV-d possessed potent protective effect against B. cinerea at 200 mg/L (72.2 %). These present findings will facilitate the design and development of novel potent fungicides.