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

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.