含1,2,3,4-四氢异喹啉片段磺酰肼和酰肼类化合物的设计、合成及生物活性研究

In order to find agricultural fungicide candidates with lassase as potential target, 14 unreported sulfonyl hydrazide and 9 hydrazide derivatives were designed and synthesized by replacing tetrahydroquinoline skeleton of the lead compound 4-methyl-N'-(1,2,3,4-tetrahydroquinoline-1-carbonothioyl)benzenesulfonohydrazide (4bg) with active fragment 1,2,3,4-tetra-hydroisoquinoline. The structures of the target compounds were confirmed by H-1 NMR, C-13 NMR and HRMS. The in vitro bioassay showed that 2-methyl-N'-(1,2,3,4-tetrahydroisoquinoline-2-carbonothioyl)benzenesulfonohydrazide (4b) showed excellent fungicidal activity against V. Mali and S. sclerotiorum with EC50 values of 4.81 and 1.57 mu g/mL, respectively, which were better than that of lead compound 4bg. In addition, 5-methyl-N'-(1,2,3,4-tetrahydroisoquinoline-2-carbonothioyl)pyrazine2-carbohydrazide (5i) showed good broad-spectrum fungicidal activity against V. Mali, S. sclerotiorum, B. cinerea, M. oryzae and F. graminearum with EC50 range of 12.88 similar to 28.65 mu g/mL. Moreover, compounds 4b and 5i exhibited moderate laccase inhibitory activity (37.07%, 35.49%), which were similar to that of cysteine (43.10%) at 50 mu g/mL. Furthermore, the binding modes of compounds 4b and 5i with laccase protein were simulated by molecular docking method, which provided guidance for further modification of compounds.