Discovery of Novel Pyrazole Amides as Potent Fungicide Candidates and Evaluation of Their Mode of Action

Abstract

A rational molecule design strategy based on scaffold hopping was applied to discover novel leads, and then a series of novel pyrazole amide derivatives were designed, synthesized, characterized, and evaluated for their antifungal activities. Bioassay results indicated that some target compounds such as S3, S12, and S26 showed good in vivo antifungal activities; among them, S26 exhibited commendable in vivo protective activity with an 89% inhibition rate against Botrytis cinerea on cucumber at 100 μg/mL that is comparable to positive controls boscalid, isopyrazam, and fluxapyroxad. Microscopy observations suggested that S26 affects the normal fungal growth. Fluorescence quenching analysis and SDH (succinate dehydrogenase) enzymatic inhibition studies validated that S26 may not be an SDH inhibitor. Based on induction of plant defense responses testing, S26 enhanced the accumulation of RBOH, WRKY6, WRKY30, PR1, and PAL defense-related genes expression and the defense-associated enzyme phenylalanine ammonia lyase (PAL) expression on cucumber. These findings support that S26 not only displayed direct fungicidal activity but also exhibited plant innate immunity stimulation activity, and it could be used as a promising plant defense-related fungicide candidate.

Synthesis and Anti‐Fungal/Oomycete Activity of Novel Sulfonamide Derivatives Containing Camphor Scaffold

“…Sun et al. synthesized novel pyrazole amides derivatives containing diphenyl ether groups [26] . The in vivo bioassay demonstrated that the most active compound presented protective activity with 89 % inhibition rate against B. cinerea .…”

“…Sun et al synthesized novel pyrazole amides derivatives containing diphenyl ether groups. [26] The in vivo bioassay demonstrated that the most active compound presented protective activity with 89 % inhibition rate against B. cinerea. Meanwhile, Wen et al [27] reported a series of nicotinamide derivatives containing diphenyl ether groups, the active compound exhibited strong activity against R. solani (EC 50 = 0.010 mg/L).…”

Design, Synthesis, and Evaluation of Novel 4-Chloropyrazole-Based Pyridines as Potent Fungicide Candidates

“…The in vitro antifungal activities of the target compounds against Fusarium oxysporum, Fusarium graminearum, Rhizoctonia cerealis, Sclerotinia sclerotiorum, Rhizoctonia solani, Alternaria solani, Gibberella zeae, Botrytis cinerea, Cercospora arachidicola, and Pyricularia oryzae were evaluated at 50 μg/mL according to the established methods . A blank solution without any test compounds was used as a blank control, and triadimefon and imazalil were selected as the positive controls.…”

“…The in vitro antifungal activities of the target compounds against Fusarium oxysporum, Fusarium graminearum, Rhizoctonia cerealis, Sclerotinia sclerotiorum, Rhizoctonia solani, Alternaria solani, Gibberella zeae, Botrytis cinerea, Cercospora arachidicola, and Pyricularia oryzae were evaluated at 50 μg/mL according to the established methods. 29 A blank solution without any test compounds was used as a blank control, and triadimefon and imazalil were selected as the positive controls. To further explore the potential fungicidal abilities of active compounds, any compounds with more than 80% or better growth inhibition activities at this concentration were evaluated to obtain their median effective concentration (EC 50 ) values.…”

Synthesis, biological activity and toxicity to zebrafish of benzamides substituted with pyrazole-linked 1,2,4-oxadiazole

“…Among them, possessing the advantages of variable structure, high-selectivity, high-efficiency, and low-toxicity and in line with the development concept of modern green pesticides, pyrazole derivatives have become the focus in the eld of pesticides. In addition, pyrazole amide derivatives have good insecticidal, [1][2][3][4][5][6][7] fungicidal [8][9][10][11][12][13][14][15][16] and other biological activities. 17 Developed in recent years, pyrazole amide derivatives, such as furametpyr, penthiopyrad, bixafen, sedaxane, penufen, chlorantraniliprole, cyantraniliprole and tebufenpyrad (Fig.…”