[
2008]
"The pine wood nematode (PWN), Bursaphelenchus xylophilus, is a mycophagous and phytophagous pathogen responsible for the current widespread epidemic of pine wilt disease, which has become a major threat to pine forests and a socioeconomic burden in Eastern Asia, North America, and some parts of Europe. No therapeutic drug for eradication of PWN currently exists. In addition, although several preventive chemical agents are currently available (e.g., morantel tartarate, avermectin, emamectin benzoate), each is associated with drawbacks (e.g., poor water solubility, efficacy, and specificity) that limit their use as of trunk-injection agents against PWN. Ideal trunk-injection drugs against PWN would be highly water-soluble and possess both nematocidal and antifungal activity (against blue stain fungi, the food source of PWN). To search for such a multifunctional nematocidal agent, we first established a high-throughput screening method, which yields potential hits within 6 hours. Using this high-throughput method, we screened of a large set of antifungal chemical libraries for agents with antinematodal activity. Among the compounds identified was HWY-4213 (1-n-undecyl-2-(2-fluorphenyl)methyl-3,4-dihydro-6,7-dimethoxy-isoquinolinium chloride), a water-soluble agent that exhibited potent antifungal and nematocidal activity. The potent nematocidal activity of this compound was confirmed with cotton ball assays. Further development of HWY-4213 as a therapeutic and preventive trunk injection agent against PWN is warranted. (Supported by a grant from a Forest Science & Technology Project [No. S110707L0501501 to YKP] through the Korea Forest Service)"