摘要/Abstract

丙酮酸脱羧酶是连接糖酵解与三羧酸循环的关键酶，目前尚无以丙酮酸脱羧酶（PDHc-E1）为靶标的杀菌剂.拟通过设计针对微生物PDHc-E1的抑制剂来获得具有杀菌活性的化合物.以课题组前期发现的E.coli PDHc-E1抑制剂L为先导化合物进行结构修饰，通过肼与醛的缩合反应合成了14个新型含腙结构单元的氨基嘧啶衍生物I作为潜在的PDHc-E1抑制剂.发现2-甲基-4-氨基-5-（甲基-4-溴苯腙）-嘧啶（I-6）不仅对E.coli PDHc-E1显示较好的活性（IC₅₀＝26.45 μmol/L），同时对真菌花生褐斑（EC₅₀ 14.11μg/mL）和苹果轮纹（EC₅₀ 0.64 μg/mL）显示了高效活性，具有进一步研究的价值.由此，通过对先导结构2-甲基-4-氨基嘧啶衍生物L中的桥键进行结构修饰，获得了对E.coli PDHc-E1具有抑制作用的高效杀菌活性的化合物.
关键词: 丙酮酸脱羧酶, 杀菌剂, 先导化合物, 2-甲基-4-氨基嘧啶衍生物
Pyruvate dehydrogenase multienzyme complex (PDHc) is a key enzyme linking glycolysis and the tricarboxylic acid cycle. Currently, there is no fungicide targeting pyruvate decarboxylase (PDHc-E1), the purpose of this study was to obtain compounds with bactericidal activity by designing inhibitors against PDHc-E1. On the basis of lead compound L, fourteen novel aminopyrimidine derivatives I were designed and synthesized by the condensation reaction of hydrazine and aldehydes as potential PDHc-E1 inhibitors. The most effective 5-((2-(4-bromophenyl)hydrazono)methyl)-2-methylpyridin-4-amine (I-6) with good E. coli PDHc-E1 enzyme inhibitory activity (IC₅₀=26.45 μmol/L) exhibited most powerful inhibitory potency against Cercospora arachidicola Hori (EC₅₀ 14.11 μg/mL) and Physalospora piricola Nose (EC₅₀ 0.64 μg/mL). Therefore it could obtain the compound with antifungal activity against microorganism PDHc-E1 enzyme by modifying the bridged linkage in lead structure 2-methyl-4-amino-pyrimidine derivatives L.
Key words: PDHc-E1, fungicide, lead compound, 2-methyl-4-amino-pyrimidine derivatives


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