Design, synthesis, molecular docking and antimicrobial evaluation of benzoylurea derivatives containing difluoromethyl (trifluoromethyl) pyrimidine.

Background: The reduction in agricultural product quality and yield caused by fungal and bacterial plant diseases has led to considerable economic losses in global crop production and poses a threat to human health. The primary method of control remains the use of chemical agents. In an effort to develop novel and highly effective antimicrobial agents, a series of benzoylurea derivatives incorporating a difluoromethyl (trifluoromethyl) pyrimidine structure were designed and synthesized.

Results: In this study, we designed and synthesized a series of novel benzoylurea derivatives containing difluoromethyl (trifluoromethyl) pyrimidine fragments. Several of the synthesized compounds exhibited notable antifungal activity in vitro against PS, CBC, BBC and TBC. Their efficacy surpassed that of the positive controls HM and Pyr. Notably, 6s demonstrated an EC value of 4.10 μg mL, significantly lower than the 31.25 μg mL for Pyr. In antibacterial assays, 6s also showed an 87.49% inhibition rate against Xoc. Moreover, in vivo tests against CBC revealed a protective efficacy of 59.39% at a concentration of 25 μg mL. Molecular docking simulations further supported its strong activity. To explore the mechanism of action of 6s on CBC, we conducted scanning electron microscopy, succinate dehydrogenase enzyme assays, and measurements of dry weight, membrane permeability, cellular contents, and ROS.

Conclusion: This study underscores the potential of benzoylurea derivatives containing difluoromethyl (trifluoromethyl) pyrimidine fragments as lead compounds for the management of CBC. The results offer important insights and pave the way for the development of novel fungicides, contributing to improved crop protection strategies in agriculture. © 2024 Society of Chemical Industry.