新型吡啶并[4,3-d]嘧啶衍生物作为潜在的甾醇 14α-脱甲基酶抑制剂的设计、合成、抑制活性及分子模拟。
Novel Pyrido[4,3-]pyrimidine Derivatives as Potential Sterol 14α-Demethylase Inhibitors: Design, Synthesis, Inhibitory Activity, and Molecular Modeling.
机构信息
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.
出版信息
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。
Zotero 插件