Studies on the novel pyridine sulfide containing SDH based heterocyclic amide fungicide

Abstract

BACKGROUND: Succinate dehydrogenase (SDH) has been identified as one of the most significant targets for fungicide discovery. To date, 23 commercial SDH inhibitor (SDHI) fungicides have been approved for plant protection since the first launch of carboxin in 1966, and extensively applied to combat destructive plant fungi. RESULTS:In this project, 20 novel pyridine sulfide derivatives containing SDH-based heterocyclic amide fungicide were designed, synthesized, and characterized by proton nuclear magnetic resonance ( 1 H-NMR), carbon-13 ( 13 C)-NMR and highresolution mass spectrometry (HRMS). In vitro fungicidal activity experiment, the target compound I-1 displayed excellent inhibitory rates against the common agricultural pathogens with half maximal effective concentration (EC 50 ) values of 5.2 to 39.8 ∼g mL −1 . The in vivo fungicidal activities demonstrated that the compound I-1 could effectively prevent Botrytis cinerea from infecting tomato and cucumber leaves with the preventative rates of 67% and 50%. The mitochondrial membrane potential detection, SDH enzyme assay and the molecular docking simulation revealed that the mechanism of action of the compound I-1 and the relevant interactions with the target enzyme may be similar to those of the control fluopyram.CONCLUSION: The biological activity screening and validation of mechanism of action indicated that the compound I-1 could be identified as a potential SDH inhibitor for further study.

Synthesis and fungicidal activity of novel benzimidazole derivatives bearing pyrimidine‐thioether moiety against Botrytis cinerea

“…16 In addition, amide structure is widely used in the discovery of pesticides and medicines because the introduction of an amide group to drug molecules can enhance the interaction with receptors, and many amide compounds exhibit significant insecticidal, herbicidal, fungicidal, anticancer, and other bioactivities. [17][18][19] Fenoxanil, mandipropamid, boscalid and fluxapyroxad, for instance, are efficient fungicides. 16 However, the thioether moiety in drug molecules might decrease the lipophilicity and increase the opportunity for hydrogen bond between drug and target enzyme, which is beneficial to enhance the affinity and improve the bioactivity.…”

Recent achievements on the agricultural applications of thioether derivatives: A 2010–2020 decade in review

“…The structures of compounds [36][37][38][39] In 2020, a series of structurally novel 1,3,4-oxadiazole thioether derivatives (46-48, Figure 10) were designed and synthesized by Shi et al [57] and Song et al [58], and bioassay results showed that compound 46 revealed better activity against G. zeae (61.6%), which was superior to that of Hymexazol, compound 47 displayed the best bioassay against U. viciae-fabae (77%) at 100 μg/mL than those of Streptochlorin and Pimprinine, and compound 48 had an inhibitory rate (99%) at 20 μg/mL against P. dissimile, which was equal to that of Streptochlorin. Hua et al [59] synthesized a series of novel thioether derivatives bearing a pyridine moiety and evaluated for their in vitro fungicidal activities against G. zeae, R. solani, C. circumscissa, P. piricola, A. kikuchiana, B. cinerea, C. capsici, and P. melongenae. Among them, compound 49 (Figure 10) displayed excellent inhibitory rates against R. solani and C. circumscissa, with EC 50 values of 37.66 and 35.30 μg/mL, respectively, which were better than those of Fluopyram.…”

Research on Crystal Structure and Fungicidal Activity of the Amide Derivatives Based on the Natural Products Sinapic Acid and Mycophenolic Acid

“…(AS). e in vivo fungicidal activity of compounds I-5 and II-4 against Physalospora piricola was performed on apples referring to literature methods [23].…”