A research team from the College of Chemistry at Huazhong Agricultural University (HZAU) has made significant progress in the design of targeted chiral agrochemicals, publishing a study in the prestigious journal Advanced Science.

The paper, titled One-Pot Synthesis of Chiral Succinate Dehydrogenase Inhibitors and Antifungal Activity Studies, details the development of a new class of chiral antifungal lead compounds and the molecular basis of their enantioselective bioactivity.

Fungal diseases account for up to 80 percent of crop losses and remain a major challenge in agriculture. Although chemical pesticides are effective, they also bring issues such as resistance, environmental harm, and food safety risks. In this context, targeted chiral pesticides are emerging as a promising green solution for efficient and precise crop protection.

Focusing on succinate dehydrogenase (SDH), a key mitochondrial target in fungi, the team used computer-aided drug design and molecular simulation to construct a chiral pharmacophore model. Among the synthesized compounds, enantiomers of compound 5f showed striking activity differences, with (S)-5f being 12-80 times more effective than its (R)-form across multiple crop pathogens.

Enantiomers of chiral antifungal molecules exhibit significant differences in biological activity. [Photo/news.hzau.edu.cn]

The study also revealed the underlying molecular mechanisms, including differences in target binding affinity and disruption of fungal cell wall structure. Additionally, the team developed a highly efficient and stereoselective synthesis method for these chiral molecules, scalable for industrial application and adaptable to commercial SDHI fungicides.