2. Academic Validation
  3. Design, Synthesis, Bioactivity, and Tentative Exploration of Action Mode for Benzyl Ester-Containing Derivatives

Design, Synthesis, Bioactivity, and Tentative Exploration of Action Mode for Benzyl Ester-Containing Derivatives

  • J Agric Food Chem. 2024 Jul 10. doi: 10.1021/acs.jafc.4c01033.
Qinglong Yuan 1,  Wen Fu 1 2,  Xiaoyan Li 3,  Zhiping Xu 1,  Xili Liu 4 5,  Zhong Li 1 6,  Xusheng Shao 1 6 7 8
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
  • 2 National Key Laboratory of Green Pesticide, Guizhou University, Guiyang 550025, Guizhou, China.
  • 3 College of Humanities and Economic Management, Yantai Institute of China Agricultural University, Yantai 264670, Shandong, China.
  • 4 State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, College of Plant Protection, Northwest A&F University, Yangling 712100, Shaanxi, China.
  • 5 Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China.
  • 6 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
  • 7 Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
  • 8 Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
PMID: 38985656 DOI: 10.1021/acs.jafc.4c01033
Abstract

The active splicing strategy has witnessed improvement in bioactivity and Antifungal spectra in pesticide discovery. Herein, a series of simple-structured molecules (Y1-Y53) containing chloro-substituted benzyl esters were designed using the above strategy. The structure-activity relationship (SAR) analysis demonstrated that the fatty acid fragment-structured esters were more effective than those containing an aromatic acid moiety or naphthenic acid part. Compounds Y36 and Y41, which featured a thiazole-4-acid moiety and trifluoromethyl aliphatic acid part, respectively, exhibited excellent in vivo curative activity (89.4%, 100 mg/L Y36) and in vitro fungicidal activity (EC50 = 0.708 mg/L, Y41) against Botrytis cinerea. Determination of Antifungal spectra and analysis of scanning electron microscopy (SEM), membrane permeability, cell peroxidation, ergosterol content, oxalic acid pathways, and enzymatic assays were performed separately here. Compound Y41 is cost effective due to its simple structure and shows promise as a disease control candidate. In addition, Y41 might act on a novel target through a new pathway that disrupts the cell membrane integrity by inducing cell peroxidation.

Keywords

action mode; active splicing; antifungal activity; benzyl ester; structure−activity relationships.

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