2. Academic Validation
  3. Discovery of Novel Rhizoctonia solani DHFR Inhibitors as Fungicides Using Virtual Screening

Discovery of Novel Rhizoctonia solani DHFR Inhibitors as Fungicides Using Virtual Screening

  • J Agric Food Chem. 2023 Dec 13;71(49):19385-19395. doi: 10.1021/acs.jafc.3c05216.
Ruirui Feng 1,  Bo Sun 2,  Shengkai Zhang 3,  Erzheng Su 4,  Andrey Kovalevsky 5,  Feng Zhang 6,  Brad C Bennett 7,  Qirong Shen 2,  Qun Wan 2
Affiliations

Affiliations

  • 1 College of Science, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
  • 2 Key Lab of Organic-Based Fertilizers of China and Jiangsu Provincial Key Lab for Solid Organic Waste Utilization, Joint International Research Laboratory of Soil Health, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
  • 3 Institute of Advanced Science Facilities, Shenzhen 518107, People's Republic of China.
  • 4 College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing 210037, People's Republic of China.
  • 5 Neutron Scattering Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831, United States.
  • 6 State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing 210095, People's Republic of China.
  • 7 Biological and Environmental Science Department, Samford University, Birmingham, Alabama 35229, United States.
PMID: 38038282 DOI: 10.1021/acs.jafc.3c05216
Abstract

Dihydrofolate reductase (DHFR) is an essential Enzyme in the folate pathway and has been recognized as a well-known target for Antibacterial and Antifungal drugs. We discovered eight compounds from the ZINC database using virtual screening to inhibit Rhizoctonia solani (R. solani), a Fungal pathogen in crops. These compounds were evaluated with in vitro assays for enzymatic and Antifungal activity. Among these, compound Hit8 is the most active R. solani DHFR inhibitor, with the IC50 of 10.2 μM. The selectivity of inhibition is 22.3 against human DHFR with the IC50 of 227.7 μM. Moreover, Hit8 has higher Antifungal activity against R. solani (EC50 of 38.2 mg L-1) compared with validamycin A (EC50 of 67.6 mg L-1), a well-documented fungicide. These results suggest that Hit8 may be a potential fungicide. Our study exemplifies a computer-aided method to discover novel inhibitors that could target plant pathogenic fungi.

Keywords

dihydrofolate reductase; enzyme inhibition; fungicide; virtual screening.

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