Design, Synthesis, and Assessment of Fungicidal Activity of Active Substructure 1,2,4-Triazole Containing Coumarin

被引:1
|
作者
Lv, You [1 ,2 ]
Li, Kun [2 ,3 ]
Lei, Liu [4 ]
Yu, Zhenwu [2 ,3 ]
Wu, Rongzhang [2 ,3 ]
Chen, Angkun [2 ,3 ]
Tian, Ruixi [2 ,3 ]
Deng, Yuxuan [2 ,3 ]
Tang, Liangfu [2 ,3 ]
Fan, Zhijin [2 ,3 ]
机构
[1] Heze Univ, Coll Agr & Biol Engn, Heze 274015, Shandong, Peoples R China
[2] Nankai Univ, Coll Chem, State Key Lab Elemento Organ Chem, Tianjin 300071, Peoples R China
[3] Nankai Univ, Coll Chem, Frontiers Sci Ctr New Organ Matter, Tianjin 300071, Peoples R China
[4] Tianjin Acad Agr Sci, Inst Agroprod Safety & Nutr, Tianjin 300381, Peoples R China
基金
中国国家自然科学基金;
关键词
Fusarium graminearum; coumarin; 1,2,4-triazole; 14-alpha demethylase; fungicidal activity; DISCOVERY;
D O I
10.1021/acs.jafc.4c07227
中图分类号
S [农业科学];
学科分类号
09 ;
摘要
Fragment splicing and molecular docking are important techniques in the design of new agrochemicals. Based on our former discovery of 4-(3,4-dichloroisothiazole)-7-hydroxycumarins 1a and 1b as fungicidal leads, following fragment splicing and molecular docking, a series of bioactive substructure 1,2,4-triazole containing coumarins were designed and synthesized. In vitro fungicidal bioassay indicated that compound 7e was more active than 1b against Botrytis cinereal, Cercospora arachidicola, and Sclerotinia sclerotiorum, with a corresponding EC50 value of 4.02 vs 5.90, 6.03 vs 8.31, and 3.81 vs 5.37 mu g/mL, respectively. Compound 7e also showed an EC50 value of 4.15 mu g/mL against Fusarium graminearum. Moreover, compound 7e demonstrated a stronger inhibition than flutriafol against F. graminearum 14-alpha demethylase, with an IC50 value of 0.59 and 0.97 mu M, respectively. Calculation results based on density functional theory calculation (DFT), molecular dynamics (MD), and molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) studies gave a rational explanation between the activity of compound 7e and its structure. This study demonstrates that fragment splicing of 1,2,4-triazole and coumarin is a good technique for discovering a novel fungicide lead.
引用
收藏
页码:27075 / 27083
页数:9
相关论文
共 50 条
  • [1] Synthesis and fungicidal activity of novel 1,2,4-triazole derivatives containing a pyrimidine moiety
    Wu, Wen-Neng
    Jiang, Yang-Ming
    Qiang-Fei
    Hai-Tang Du
    PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS, 2019, 194 (12) : 1171 - 1175
  • [2] Synthesis and Fungicidal Activity of 1,2,4-Triazole Derivatives Containing 2-Fluorophenyl Moiety
    Tong, Jianying
    Shi, Yanxia
    Liu, Xinghai
    Sun, Nabo
    Li, Baoju
    CHINESE JOURNAL OF ORGANIC CHEMISTRY, 2012, 32 (12) : 2373 - 2377
  • [3] Design, Synthesis and Fungicidal Activity of New 1,2,4-Triazole Derivatives Containing Oxime Ether and Phenoxyl Pyridinyl Moiety
    Bai, Hui
    Liu, Xuelian
    Chenzhang, Pengfei
    Xiao, Yumei
    Fu, Bin
    Qin, Zhaohai
    MOLECULES, 2020, 25 (24):
  • [4] Design, synthesis and fungicidal activity of novel strobilurin-1,2,4-triazole derivatives containing furan or thiophene rings
    Yang Liu
    Ming Liu
    Dongkai Zhang
    Xuewen Hua
    Baolei Wang
    Sha Zhou
    Zhengming Li
    Chemical Research in Chinese Universities, 2016, 32 : 952 - 958
  • [5] Design, Synthesis and Fungicidal Activity of Novel Strobilurin-1,2,4-Triazole Derivatives Containing Furan or Thiophene Rings
    Liu Yang
    Liu Ming
    Zhang Dongkai
    Hua Xuewen
    Wang Baolei
    Zhou Sha
    Li Zhengming
    CHEMICAL RESEARCH IN CHINESE UNIVERSITIES, 2016, 32 (06): : 952 - 958
  • [6] Synthesis and insecticidal activity of novel 1,2,4-triazole containing amidine moiety
    Zhao, Fenghai
    Liu, Yanfei
    Qin, Zhaohai
    Wu, Yanhua
    Xiao, Yumei
    Li, Jia-Qi
    JOURNAL OF HETEROCYCLIC CHEMISTRY, 2022, 59 (10) : 1723 - 1735
  • [7] Synthesis and Herbicidal Activity of 1,2,4-Triazole Derivatives Containing a Pyrazole Moiety
    Mu, Jin-Xia
    Zhai, Zhi-Wen
    Tan, Cheng-Xia
    Weng, Jian-Quan
    Wu, Hong-Ke
    Duke, Stephen O.
    Zhang, Yong-Gang
    Liu, Xing-Hai
    JOURNAL OF HETEROCYCLIC CHEMISTRY, 2019, 56 (03) : 968 - 971
  • [8] Synthesis and Fungicidal Activities of Novel Quinazoline Derivatives Containing 1,2,4-Triazole Schiff-Base Unit
    Liu, Junhu
    Liu, Yong
    Jian, Junyou
    Bao, Xiaoping
    CHINESE JOURNAL OF ORGANIC CHEMISTRY, 2013, 33 (02) : 370 - 374
  • [9] Synthesis and Biological Activity of 1,2,4-Triazole Thioether Derivatives Containing Pyrazole Moiety
    Zhai, Zhiwen
    Wang, Qiao
    Shen, Zhonghua
    Tan, Chengxia
    Weng, Jianquan
    Liu, Xinghai
    CHINESE JOURNAL OF ORGANIC CHEMISTRY, 2017, 37 (01) : 232 - 236
  • [10] Synthesis and Biological Activity of Some Novel Trifluoromethyl-Substituted 1,2,4-Triazole and Bis(1,2,4-Triazole) Mannich Bases Containing Piperazine Rings
    Wang, Bao-Lei
    Shi, Yan-Xia
    Ma, Yi
    Liu, Xing-Hai
    Li, Yong-Hong
    Song, Hai-Bin
    Li, Bao-Ju
    Li, Zheng-Ming
    JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2010, 58 (09) : 5515 - 5522