BACKGROUNDThe 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.RESULTSIn 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 EC50 value of 4.10 μg mL−1, significantly lower than the 31.25 μg mL−1 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−1. 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.CONCLUSIONThis 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.

中文翻译：

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含二氟甲基（三氟甲基）嘧啶的苯甲酰脲衍生物的设计、合成、分子对接和抗菌评价


背景真菌和细菌性植物病害导致农产品质量和产量下降，导致全球作物生产遭受了相当大的经济损失，并对人类健康构成威胁。控制的主要方法仍然是使用化学试剂。为了开发新型高效的抗菌剂，设计并合成了一系列结合二氟甲基（三氟甲基）嘧啶结构的苯甲酰脲衍生物。结果本研究设计合成了一系列含有二氟甲基 （trifluoromethyl） 嘧啶片段的新型苯甲酰脲衍生物。几种合成的化合物在体外对 PS、CBC、BBC 和 TBC 表现出显着的抗真菌活性。它们的疗效超过了阳性对照 HM 和 Pyr。值得注意的是，6s 的 EC50 值为 4.10 μg mL-1，显著低于 Pyr 的 31.25 μg mL-1。在抗菌试验中，6s 对 Xoc 的抑制率也为 87.49%。此外，针对 CBC 的体内测试显示，在 25 μg mL-1 浓度下，保护功效为 59.39%。分子对接模拟进一步支持了其强大的活性。为了探索 6s 对 CBC 的作用机制，我们进行了扫描电子显微镜、琥珀酸脱氢酶测定以及干重、膜通透性、细胞内容物和 ROS 的测量。结论该研究强调了含有二氟甲基（三氟甲基）嘧啶片段的苯甲酰脲衍生物作为先导化合物治疗 CBC 的潜力。结果提供了重要的见解，并为新型杀菌剂的开发铺平了道路，有助于改进农业作物保护策略。© 2024 化工学会.