Journal of Integrative Agriculture ›› 2024, Vol. 23 ›› Issue (4): 1259-1273.DOI: 10.1016/j.jia.2023.05.031

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新型四氢β-咔啉衍生物的发现和构效关系研究及其作为凋亡诱导剂控制植物细菌性病害

  

  • 收稿日期:2023-01-06 接受日期:2023-04-12 出版日期:2024-04-20 发布日期:2024-03-30

Discovery and structure-activity relationship studies of novel tetrahydro-β-carboline derivatives as apoptosis initiators for treating bacterial infections

Shanshan Su, Hongwu Liu, Junrong Zhang, Puying Qi, Yue Ding, Ling Zhang, Linli Yang, Liwei Liu, Xiang Zhou#, Song Yang#   

  1. National Key Laboratory of Green Pesticide/Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education/Center for R&D of Fine Chemicals, Guizhou University, Guiyang 550025, China

  • Received:2023-01-06 Accepted:2023-04-12 Online:2024-04-20 Published:2024-03-30
  • About author:Shanshan Su, E-mail: sss132247@163.com; #Correspondence Song Yang, Tel: +86-851-88292171, E-mail: jhzx.msm@gmail.com; Xiang Zhou, Tel: +86-851-88292170, E-mail: xiangzhou@gzu.edu.cn
  • Supported by:
    We acknowledge the supports from National Natural Science Foundation of China (21877021, 32160661, and 32202359), the Guizhou Provincial S&T Project, China (2018[4007]), the the Guizhou Province, China [Qianjiaohe KY number (2020)004], the Program of Introducing Talents of Discipline to Universities of China (D20023, 111 Program), and the Guizhou University (GZU) Found for Newly Enrolled Talent, China (202229).

摘要:

开发高活性、环境友好的绿色新农药是保护农作物健康和食品安全的重要手段。为了发现新的候选杀菌剂,本研究论文采用Pictet–Spengler反应制备了一系列新颖的1,2,3,4-四氢-β-咔啉(THC)衍生物,并评估了其对水稻白叶枯病菌Xoo)、柑橘溃疡病菌Xac)和猕猴桃溃疡病菌Psa)的离体活体生物活性结果表明,大多数目标化合物对三种植物病原都表现出良好的生物活性。其中,化合物A17水稻白叶枯病菌柑橘溃疡病菌表现优异抑菌活性,其EC50值分别为7.27 mg mL-14.89 mg mL-1化合物A8猕猴桃溃疡病菌显示出好的抑制活性,其EC50值为4.87 mg mL-1此外,在200 mg mL-1浓度下,化合物A17水稻白叶枯病(52.67%)柑橘溃疡病(79.79%)表现出优异的防治效果,化合物A8猕猴桃溃疡病的防治效果为84.31%构效关系研究表明:THCA环的C6位无取代基时有利于提高其抑菌活性;对于 THCC环,当N2位是NH基团是有利于提高其抑菌活性;此外,THCC环的NH位置引入长链可以增强其抗菌活性。通过大量的生物学实验验证,THC衍生物能扰乱细菌体内的氧化还原系统,造成细菌活性氧的爆发细胞膜的破坏,最终导致细菌的死亡。上述的研究工作为以THC为活性骨架的新型杀菌剂创制提供了重要参考

Abstract: Developing and excavating new agrochemicals with highly active and safe is an important tactic for protecting crop health and food safety.  In this paper, to discover the new bactericide candidates, we designed, prepared a new type of 1,2,3,4-tetrahydro-carboline (THC) derivatives and evaluated the in vitro and in vivo bioactivities against the Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa).  The in vitro bioassay results exhibited that most title molecules possessed good activity toward the three plant pathogenic bacteria, the compound A17 showed the most active against Xoo and Xac with EC50 values of 7.27 and 4.89 mg mL–1 respectively, and compound A8 exhibited the best inhibitory activity against Psa with EC50 value of 4.87 mg mL–1.  Pot experiments showed that compound A17 exhibited excellent in vivo antibacterial activities to manage rice bacterial leaf blight and citrus bacterial canker, with protective efficiencies of 52.67 and 79.79% at 200 mg mL–1, respectively.  Meanwhile, compound A8 showed good control efficiency (84.31%) against kiwifruit bacterial canker at 200 mg mL–1.  Antibacterial mechanism suggested that these compounds could interfere with the balance of the redox system, damage the cell membrane, and induce the apoptosis of Xoo cells.  Taken together, our study revealed that tetrahydro-β-carboline derivatives could be a promising candidate model for novel broad-spectrum bactericides.

Key words: tetrahydro-β-carboline derivatives ,  antibacterial activity ,  ROS ,  cell apoptosis