Abstract：
Natural products, known for their environmental safety, are regarded as a significant basis for the modification and advancement of fungicides. Melatonin, as a low-cost natural indole, exhibits diverse biological functions, including antifungal activity. However, its potential as an antifungal agent has not been fully explored. In this study, a series of melatonin derivatives targeting the mitogen-activated protein kinase (Mps1) protein of fungal pathogens were synthesized based on properties of melatonin, among which the trifluoromethyl-substituted derivative Mt-23 exhibited antifungal activity against seven plant pathogenic fungi, and effectively reduced the severity of crop diseases, including rice blast, Fusarium head blight of wheat and gray mold of tomato. In particular, its EC50 (5.4 µM) against the rice blast fungus Magnaporthe oryzae is only one-fourth that of isoprothiolane (22 µM), a commercial fungicide. Comparative analyzes revealed that Mt-23 simultaneously targets the conserved protein kinase Mps1 and lipid protein Cap20. Surface plasmon resonance assays showed that Mt-23 directly binds to Mps1 and Cap20. In this study, we provide a strategy for developing antifungal agents by modifying melatonin, and the resultant melatonin derivative Mt-23 is a commercially valuable, eco-friendly and broad-spectrum antifungal agent to combat crop disease.
摘要：
天然产品,以他们的环境安全而闻名，被认为是杀菌剂改性和进步的重要基础。褪黑激素,作为一种低成本的天然吲哚，表现出不同的生物学功能，包括抗真菌活性。然而,其作为抗真菌剂的潜力尚未得到充分探索。在这项研究中,根据褪黑素的性质，合成了一系列针对真菌病原体丝裂原活化蛋白激酶（Mps1）蛋白的褪黑素衍生物，其中三氟甲基取代的衍生物Mt-23对7种植物病原真菌具有抗真菌活性，并有效降低了作物病害的严重程度，包括稻瘟病,小麦枯萎病和番茄灰霉病。特别是,其对稻瘟病菌稻瘟病菌的EC50（5.4µM）仅是异丙硫烷（22µM）的四分之一，一种商业杀菌剂。比较分析表明，Mt-23同时靶向保守的蛋白激酶Mps1和脂质蛋白Cap20。表面等离子体共振分析显示Mt-23直接结合Mpsl和Cap20。在这项研究中,我们提供了一种通过修饰褪黑激素来开发抗真菌药物的策略，所得的褪黑激素衍生物Mt-23具有商业价值，环保和广谱抗真菌剂，以对抗作物疾病。
