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.
Original language | English |
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Pages (from-to) | 19385-19395 |
Number of pages | 11 |
Journal | Journal of Agricultural and Food Chemistry |
Volume | 71 |
Issue number | 49 |
DOIs | |
State | Published - Dec 13 2023 |
Funding
We thank the support from Prof. Gang Chen, Prof. Fazhi Qi, and Dr. Yakang Li to use high-performance computation resources, including the National High Energy Physics Science Data Center (NHEPSDC) and China Spallation Neutron Source (CSNS). This work was supported by the National Natural Science Foundation of China (nos. 32071264 and 12005248) and Nanjing Agricultural University (no. XUEKEN2023039).
Funders | Funder number |
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China Spallation Neutron Source | |
National High Energy Physics Science Data Center | |
National Natural Science Foundation of China | 12005248, 32071264 |
Nanjing Agricultural University | XUEKEN2023039 |
Keywords
- dihydrofolate reductase
- enzyme inhibition
- fungicide
- virtual screening