School of Science, Xihua University, Chengdu 610039, PR China.
Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, PR China.
J Agric Food Chem. 2024 May 29;72(21):12260-12269. doi: 10.1021/acs.jafc.3c09543. Epub 2024 May 17.
Thirty-four new pyrido[4,3-]pyrimidine analogs were designed, synthesized, and characterized. The crystal structures for compounds and were measured by means of X-ray diffraction of single crystals. The bioassay results showed that most target compounds exhibited good fungicidal activities against , , , and at 16 μg/mL. Compounds , , , and possessed better fungicidal activities than the commercial fungicide epoxiconazole against . Their half maximal effective concentration (EC) values were 0.191, 0.487, 0.369, 0.586, and 0.670 μg/mL, respectively. Furthermore, the inhibitory activities of the bioactive compounds were determined against sterol 14α-demethylase (CYP51). The results displayed that they had prominent activities. Compounds , , , and also showed better inhibitory activities than epoxiconazole against CYP51. Their half maximal inhibitory concentration (IC) values were 0.219, 0.602, 0.422, 0.726, and 0.802 μg/mL, respectively. The results of molecular dynamics (MD) simulations exhibited that compounds and possessed a stronger affinity to CYP51 than epoxiconazole.
设计、合成并表征了 34 种新的吡啶并[4,3-]嘧啶类似物。通过单晶 X 射线衍射测量了化合物 和 的晶体结构。生物测定结果表明，大多数目标化合物在 16 μg/mL 时对 、 、 、 和 表现出良好的杀菌活性。化合物 、 、 、 和 对 表现出比商业杀菌剂环唑醇更好的杀菌活性。它们的半最大有效浓度（EC）值分别为 0.191、0.487、0.369、0.586 和 0.670 μg/mL。此外，还测定了生物活性化合物对甾醇 14α-脱甲基酶（CYP51）的抑制活性。结果显示它们具有显著的活性。化合物 、 、 、 和 对 CYP51 的抑制活性也优于环唑醇。它们的半最大抑制浓度（IC）值分别为 0.219、0.602、0.422、0.726 和 0.802 μg/mL。分子动力学（MD）模拟的结果表明，化合物 、 和 与 CYP51 的亲和力强于环唑醇。
