2. Academic Validation
  3. Identification of propranolol and derivatives that are chemical inhibitors of phosphatidate phosphatase as potential broad-spectrum fungicides

Identification of propranolol and derivatives that are chemical inhibitors of phosphatidate phosphatase as potential broad-spectrum fungicides

  • Plant Commun. 2023 Aug 30;100679. doi: 10.1016/j.xplc.2023.100679.
Juan Zhao 1,  Yu Chen 2,  Zhifen Ding 3,  Yaru Zhou 3,  Ruiqing Bi 3,  Ziting Qin 3,  Lei Yang 3,  Peng Sun 3,  Qiping Sun 3,  Guang Chen 4,  Daiyuan Sun 5,  Xianya Jiang 6,  Lu Zheng 3,  Xiao-Lin Chen 3,  Hu Wan 3,  Guanghui Wang 5,  Qiang Li 7,  Huailong Teng 8,  Guotian Li 9
Affiliations

Affiliations

  • 1 National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Hubei Key Laboratory of Plant Pathology, The Center of Crop Nanobiotechnology, Huazhong Agricultural University, Wuhan 430070, China; College of Chemistry and Life Sciences, Sichuan Provincial Key Laboratory for Development and Utilization of Characteristic Horticultural Biological Resources, Chengdu Normal University, Chengdu 611130, China.
  • 2 College of Science, Huazhong Agricultural University, Wuhan 430070, China.
  • 3 National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Hubei Key Laboratory of Plant Pathology, The Center of Crop Nanobiotechnology, Huazhong Agricultural University, Wuhan 430070, China.
  • 4 National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China.
  • 5 State Key Laboratory of Crop Stress Biology for Arid Areas, College of Plant Protection, Northwest A&F University, Yangling 712100, China.
  • 6 Yangjiang Institute of Agricultural Sciences, Yangjiang 529500, China.
  • 7 National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: qli@mail.hzau.edu.cn.
  • 8 College of Science, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: qli@mail.hzau.edu.cn.
  • 9 National Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Hubei Key Laboratory of Plant Pathology, The Center of Crop Nanobiotechnology, Huazhong Agricultural University, Wuhan 430070, China. Electronic address: qli@mail.hzau.edu.cn.
PMID: 37653727 DOI: 10.1016/j.xplc.2023.100679
Abstract

Plant diseases cause enormous economic losses in agriculture and threaten global food security, and application of agrochemicals is an important means to control crop diseases. Thus, exploring disease-resistant mechanisms and synthesis of highly bioactive agrochemicals are of great importance. Here, we showed that propranolol, a phosphatidate Phosphatase (Pah) inhibitor, effectively suppressed Fungal growth, sporulation, sexual reproduction, and plant Infection on diverse Plants. The MoPah1 Enzyme activity of the rice blast fungus Magnaporthe oryzae was inhibited by propranolol. Additionally, alterations in lipid metabolism were associated with inhibited hyphal growth and appressorium formation caused by propranolol in M. oryzae. Propranolol inhibited a broad-spectrum of 12 plant pathogens, effectively inhibiting Infection of barley, wheat, maize, tomato, and pear. To improve the anti-fungal capacity, we synthesized a series of propranolol derivatives, and one of them remarkably enhanced the anti-fungal ability by 16-fold by binding to MoPah1. Furthermore, propranolol and its derivatives reduced the severity of rice blast and Fusarium head blight of wheat in the field. Taken together, our study demonstrates that propranolol suppresses Fungal development and Infection through mechanisms involved in lipid metabolism. Propranolol and its derivatives could be promising candidates for fungicide development.

Keywords

Pyricularia oryzae; chemical modification; lipid metabolism; molecular designing; propranolol; virulence.

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