1. Academic Validation
  2. Discovery of a Fungicide Candidate Targeting Succinate Dehydrogenase via Computational Substitution Optimization

Discovery of a Fungicide Candidate Targeting Succinate Dehydrogenase via Computational Substitution Optimization

  • J Agric Food Chem. 2021 Nov 10;69(44):13227-13234. doi: 10.1021/acs.jafc.1c04536.
Hua Li 1 Yu-Xia Wang 1 Xiao-Lei Zhu 1 Guang-Fu Yang 1 2
Affiliations

Affiliations

  • 1 Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensor Technology and Health of Ministry of Science and Technology, Central China Normal University, Wuhan 430079, People's Republic of China.
  • 2 Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300071, People's Republic of China.
Abstract

Succinate Dehydrogenase (SDH, EC 1.3.5.1) has proven to be an important fungicidal target, and the inhibition of SDH is useful in the treatment of plant pathogens. The discovery of a novel active SDH inhibitor is of high value. Herein, we disclose the discovery of a potent, highly active inhibitor as a fungicide candidate by using a computational substitution optimization method, a fast drug design method developed in our laboratory. The greenhouse experiments showed that compound 17c exhibited high protective activity against south corn rust, soybean rust (SBR), and rice sheath blight at a very low dosage of 0.781 mg/L. Moreover, the field trials indicated that compound 17c is comparable to and even better than commercial fungicides against SBR and cucumber powdery mildew at 50 mg/L concentration. Most surprisingly, compound 17c resulted to be strictly better in curative activity than the commercial fungicide benzovindiflupyr. The computation results indicated that 17c could form another hydrogen bond with C_S42 and then lead to strong van der Waals and electronic interactions with SDH. Our results suggested that 17c is a potential fungicide candidate for SDH.

Keywords

computational substitution optimization; curative activity; diphenyl ether; fungicide; protective activity.

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