College of Plant Protection, Shenyang Agricultural University, Shenyang 110866, China.
College of Science, China Agricultural University, Beijing 100091, China.
Bioorg Chem. 2019 Jun;87:56-69. doi: 10.1016/j.bioorg.2019.03.017. Epub 2019 Mar 9.
Botrytis cinerea is an economically important fungal pathogen with a host range of over 200 plant species. Unfortunately, gray mold disease caused by B. cinerea has not been effectively controlled because of its high risk for fungicide resistance development. As a part of our ongoing efforts to develop novel sulfonamides as agricultural fungicides against Botrytis cinerea, we introduced 2-aminoethanesulfonic acid (taurine) substructure, designed and synthesized a series of novel 2-substituted acylaminoethylsulfonamides. The newly synthesized sulfonamides were evaluated in vitro and in vivo for their fungicidal activity against Botrytis cinerea, of which the 2-ethoxyacetylamide derivative (V-A-12, EC = 0.66 mg·L) exhibited the highest potency in vitro and superior fungicidal activity compared with procymidone (EC = 1.06 mg·L). In vivo bioassay indicated that compound V-A-12 could be effective for the control of tomato gray mold. Moreover, the structure-activity relationship of these sulfonamides was analyzed by establishing a three-dimensional quantitative structure-activity relationship (3D-QSAR) model, which can provide guidance for the development of sulfonamides as fungicides. Finally, the effeicacy of sulfonamide derivatives was again verified in the activity evaluation against resistant Botrytis cinerea strains. These results further enhance the development value of 2-substituted acylaminoethylsulfonamides to control the tomato gray mold.
灰葡萄孢是一种具有超过 200 种宿主植物的经济上重要的真菌病原体。不幸的是，由于其对杀菌剂产生抗性的高风险，由 B. cinerea 引起的灰霉病尚未得到有效控制。作为我们正在努力开发新型磺酰胺类农业杀菌剂以防治灰葡萄孢的一部分，我们引入了 2-氨基乙磺酸（牛磺酸）亚结构，设计并合成了一系列新型 2-取代酰氨基乙磺酰胺。新合成的磺酰胺在体外和体内对灰葡萄孢的杀菌活性进行了评估，其中 2-乙氧乙酰胺衍生物（V-A-12，EC=0.66mg·L）表现出最高的体外活性，与咯菌腈（EC=1.06mg·L）相比具有更好的杀菌活性。体内生物测定表明，化合物 V-A-12 可有效防治番茄灰霉病。此外，通过建立三维定量构效关系（3D-QSAR）模型对这些磺酰胺的构效关系进行了分析，为磺酰胺类杀菌剂的开发提供了指导。最后，再次在对抗性灰葡萄孢菌株的活性评价中验证了磺酰胺衍生物的功效。这些结果进一步增强了 2-取代酰氨基乙磺酰胺控制番茄灰霉病的开发价值。
