Discovery of quinazoline compound as a novel nematicidal scaffold

Abstract

With the aim of discovering novel nematicidal scaffolds, the nematicidal activities of a series of quinazoline compounds were tested, with some compounds showing excellent results. Among them, the LC₅₀ values of compound K11 against Bursaphelenchus xylophilus, Aphelenchoides besseyi, and Ditylenchus destructor were 7.33, 6.09, and 10.95 mg/L, respectively. In addition, the nematicidal activity of compound K11 against Meloidogyne incognita was 98.77% at 100 mg/L. Compound K11 not only increased the production of reactive oxygen species and the accumulation of lipofuscin and lipids in nematodes, but it also attenuated nematode pathogenicity by reducing the nematodes' antioxidant capacity. Transcriptomic analysis showed that compound K11 had significant effects on fatty acid degradation, metabolic pathways, and the differentially expressed genes related to redox processes in nematodes. Furthermore, the expression levels of the corresponding differentially expressed genes were verified using real-time quantitative polymerase chain reaction. Quinazoline can be used as a new nematicidal scaffold, and it is expected that more work will be done on the discovery of novel nematicides based on the lead compound K11 in the future.

Keywords: Mechanism; Nematicidal activity; Nematicides; Oxidative stress; Quinazoline scaffold.