Mitochondrion-Targeted Triphenylphosphonium-Based Kresoxim-Methyl Analogues: Synthesis, Fungicidal Activity, and Action Mechanism Approach

  • J Agric Food Chem. 2022 Oct 26;70(42):13563-13573. doi: 10.1021/acs.jafc.2c05071.
Xuelian Liu  1 ,  Dachao Tang  1 ,  Fahong Yin  1 ,  Jiayao Wang  1 ,  Xueqin Zhang  2 ,  Yumei Xiao  1 ,  Jia-Qi Li  1 ,  Zhaohai Qin  1
Affiliations
  • 1. College of Science, China Agricultural University, Beijing100193, China.
  • 2. College of Biological Sciences, China Agricultural University, Beijing100193, China.
PMID: 36223487 DOI: 10.1021/acs.jafc.2c05071
Abstract

β-Methoxyacrylate fungicides as complex III Qo site inhibitors play a crucial role in the control of crop diseases. In this study, the triphenylphosphonium (TPP)-driven mitochondrion-targeting strategy was used to modify the kresoxim-methyl scaffold at the toxicophore or side chain to develop novel mitochondrion-targeted QoI fungicides. These kresoxim-methyl analogues exhibited different fungicidal activities, depending on the position of TPP conjugation and the linker length. Among them, 2A-5 and 2C-4 showed excellent characteristics superior to kresoxim-methyl as candidate fungicides, in which the activity enhancement against Phytophthora capsici was the most remarkable, with an EC50 value of about 5 μM. Notably, both hyphal and zoospore structures of the pathogens were severely damaged after treatment with them. The action mechanism approach revealed that they might cause a significant decrease in ATP synthesis and ROS outbreak in different ways. The results also provided a new insight into the contribution of targeting group TPP to the fungicidal activity in TPP-driven fungicides.

Keywords
cytochrome bc1 complex inhibitor; fungicidal activity; kresoxim-methyl analogues; mitochondrion-targeted fungicides; triphenylphosphonium (TPP).
Products