为了发现以漆酶作为潜在靶标的农用杀菌剂候选化合物, 以天然产物四氢喹啉衍生物4-甲基-N'-(1,2,3,4-四氢喹啉-1-硫代羰基)苯磺酰肼(4bg)为先导, 引入活性片段1,2,3,4-四氢异喹啉, 设计合成了14个未见文献报道的磺酰肼类和9个酰肼类化合物. 目标物结构均经过¹H NMR、¹³C NMR、HRMS确证. 离体抑菌活性测试结果表明, 2-甲基-N'-(1,2,3,4-四氢异喹啉-2-碳硫酰基)苯磺酰肼(4b)对苹果腐烂病菌(V. mali)和油菜菌核病菌(S. sclerotiorum)均表现出显著的抑菌活性, EC₅₀分别为4.81, 1.57 μg/mL, 优于先导化合物4bg. 同时, 5-甲基-N'-(1,2,3,4-四氢异喹啉-2-碳硫酰基)吡嗪-2-甲酰肼(5i)对苹果腐烂病菌、油菜菌核病菌、番茄灰霉病菌(B. cinerea)、稻瘟病菌(M. oryzae)、小麦赤霉病菌(F. graminearum)均表现较好的抑菌活性(EC₅₀=12.88~28.65 μg/mL). 此外, 在50 μg/mL浓度下, 化合物4b和5i表现出一定的漆酶抑制活性(37.07%, 35.49%), 与阳性对照半胱氨酸(43.10%)相当. 通过分子对接的方法分析了化合物4b和5i与漆酶蛋白的结合模式, 为化合物进一步改造提供参考.

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- hydro-isoquinoline. The structures of the target compounds were confirmed by ¹H NMR, ¹³C 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 μg/mL, respectively, which were better than that of lead compound 4bg. In addition, 5-methyl-N'-(1,2,3,4-tetrahydroisoquinoline-2-carbonothioyl)pyra- zine-2-carbohydrazide (5i) showed good broad-spectrum fungicidal activity against V. Mali, S. sclerotiorum, B. cinerea, M. oryzae and F. graminearum with EC₅₀ range of 12.88~28.65 μg/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 μg/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.