Discovery of bifunctional pyrazolo[1,5-a]pyrimidine derivatives: Design, synthesis, nematicidal, and fungicidal activities.

A series of pyrazolo[1,5-a]pyrimidine derivatives were designed and synthesized by the strategy of ring splitting and combination, and their nematicidal and fungicidal activities were evaluated. Compound 11 had an LC value of 8.1 mg/L against Bursaphelenchus xylophilus (B. xylophilus), which was superior to that of tioxazafen (83.7 mg/L). Compound 11 not only inhibited the feeding, reproduction and eggs hatching abilities of B. xylophilus, but also induces adverse oxidative stress responses and severe intestinal damage in nematodes, ultimately leading to nematode death. In addition, compound 11 exhibited excellent fungicidal activity against Botryosphaeria dothidea (B. dothidea, EC = 2.0 mg/L), which was superior to that of azoxystrobin (44.9 mg/L). Meanwhile, compound 11 showed excellent in vivo fungicidal activity against five plant pathogenic fungi. Mechanistic studies have shown that compound 11 can significantly disrupt the integrity of the cell membrane, thereby increasing cell membrane permeability and inducing the release of cellular contents. Additionally, compound 11 can severely damage the surface morphology of mycelium and elevate intracellular reactive oxygen species (ROS) levels, ultimately exhibiting fungicidal activity. Therefore, compound 11 can be further studied as a potential novel bifunctional pesticide.