Discovery of hatching stimulants for Globodera pallida with simple chemical structures and their application for nematode density reduction in soil

Potato cyst nematodes (PCN), Globodera pallida and G. rostochiensis, are among the most destructive pests affecting potatoes. Hatching stimulants that induce “suicide hatching” in the absence of host plants offer a promising strategy for PCN management. However, previously identified natural hatching stimulants have complex structures, making them difficult to synthesize. Therefore, we explored hatching stimulants with simple structures to develop an effective method for PCN control. We screened 9600 compounds and identified 9 with weak G. pallida hatching-stimulation activity. To further the search, we examined 191 commercially available compounds that shared structural similarities with these 9 compounds, and discovered a compound (5,5-dimethyl-4-phenylpyrrolidin-2-one) which induced an 89% hatching rate in G. pallida juveniles at a concentration of 10 µg/ml. Further synthesis of structurally related compounds yielded several compounds that promoted high hatching rates of the nematode, including three substances that induced over 90% hatch at 10 ng/ml. However, these compounds did not stimulate hatching in G. rostochiensis. Structure-activity analysis suggested that the 5-membered ring with substituted phenyl, dimethyl, and carbonyl groups, characteristic of 5,5-dimethyl-4-phenylpyrrolidin-2-one, was crucial for hatching activity. Application of the active compound 5,5-dimethyl-4-(p-tolyl)pyrrolidin-2-one at 30 mg/m 2 in a G. pallida-infested field reduced the nematode egg density in the soil by approximately 90%. These compounds with simple structures hold great potential as effective control agents for G. pallida.