Antifungal Activity of Novel 5,6,7,8-Tetrahydroquinazolin Derivatives against Plant Pathogenic Fungi by Targeting Sterol 14α-Demethylase (CYP51) and the Application on Rice

The emergence of severe resistance issues in plant pathogenic fungi poses a significant threat to the global quality and safety of crops. In this study, 36 novel derivatives featuring a 5,6,7,8-tetrahydroquinazolin structure were designed and synthesized for the first time. These 36 target compounds were subjected to in vitro tests against five Fungal species. Specifically, compound 4r demonstrated excellent efficacy against R. solani, with EC₅₀ values of 0.33 μg/mL, compared to the positive control value of 0.78 μg/mL. Additionally, the IC₅₀ values of compounds 4r and Fluquinconazole were 0.34 and 0.62 μg/mL, respectively. The in vivo experiments further indicated that compound 4r possessed a superior action effect compared to that of Fluquinconazole. The mechanism of action of compound 4r was initially analyzed, revealing that it inhibits the production of Fungal ergosterol, 4r formed hydrophobic interactions with two more residues when compared with Fluquinconazole, and the binding energies of compound 4r and Fluquinconazole were -57.2 and -39.7 kcal/mol. The studies presented above demonstrated that 4r has a better mode of action than the positive control and could be a potential commercial fungicide candidate.

5,6,7,8-tetrahydroquinazolin; CYP51; Rhizoctonia solani; antifungal activity.