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

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journal contribution
posted on 2023-12-01, 12:39 authored by Ruirui Feng, Bo Sun, Shengkai Zhang, Erzheng Su, Andrey Kovalevsky, Feng Zhang, Brad C. Bennett, Qirong Shen, Qun Wan
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.