Bioactivity-Guided Synthesis Accelerates the Discovery of 3-(Iso)quinolinyl-4-chromenones as Potent Fungicide Candidates

作者：Wei Wang, Shan Zhang, Jianhua Wang, Furan Wu, Tao Wang, Gong Xu · 发表于：Journal of Agricultural and Food Chemistry · 年份：2020 · DOI：10.1021/acs.jafc.0c06700 · 被引用次数：60 · 研究领域：Fungal Plant Pathogen Control、Synthesis of Organic Compounds、Phytochemical compounds biological activities

Fungal infections could cause tremendous decreases in crop yield and quality. Natural products, including flavonoids and (iso)quinolines, have always been an important source for lead discovery in medicinal and agricultural chemistry. To promote the discovery and development of new fungicides, a series of 3-(iso)quinolinyl-4-chromenone derivatives was designed and synthesized by the active substructure splicing principle and evaluated for their antifungal activities. The lead optimization was guided by bioactivity. The bioassay data revealed that the 3-quinolinyl-4-chromenone 13 showed significant in vitro activities against S. sclerotiorum, V. mali, and B. cinerea with EC 50 values of 3.65, 2.61, and 2.32 mg/L, respectively. The 3-isoquinolinyl-4-chromenone 25 exhibited excellent in vitro activity against S. sclerotiorum with an EC 50 value of 1.94 mg/L, close to that of commercial fungicide chlorothalonil (EC 50 = 1.57 mg/L) but lower than that of boscalid (EC 50 = 0.67 mg/L). For V. mali and B. cinerea, 3-isoquinolinyl-4-chromenone 25 (EC 50 = 1.56, 1.54 mg/L) showed significantly higher activities than chlorothalonil (EC 50 = 11.24, 2.92 mg/L). In addition, in viv o experiments proved that compounds 13 and 25 have excellent protective fungicidal activities with inhibitory rates of 88.24 and 94.12%, respectively, against B. cinerea at 50 mg/L, while the positive controls chlorothalonil and boscalid showed inhibitory rates of 76.47 and 97.06%, respectively. Physiological an...