有机化学 ›› 2019, Vol. 39 ›› Issue (8): 2295-2302.DOI: 10.6023/cjoc201903064 上一篇    下一篇

所属专题: 陈茹玉先生诞辰100周年

研究论文

含腙结构单元的氨基嘧啶衍生物的合成与生物活性研究

何海峰b, 夏芹a, 贺红武a   

  1. a 华中师范大学化学学院 农药与化学生物学教育部重点实验室 武汉 430079;
    b 江西科技师范大学化学化工学院 南昌 330046
  • 收稿日期:2019-03-27 修回日期:2019-05-12 出版日期:2019-08-25 发布日期:2019-06-06
  • 通讯作者: 贺红武 E-mail:he1208@mail.ccnu.edu.cn
  • 基金资助:

    国家自然科学基金(Nos.21877047,21867011)、江西省教育科技厅基金(No.GJJ170672)资助项目.

Synthesis and Biological Evaluation of Pyrimidine Derivatives Containing Hydrazine Structural Unit

He Haifengb, Xia Qina, He Hongwua   

  1. a Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079;
    b School of Chemistry and Chemical Engineering, Jiangxi Science and Technology Normal University, Nanchang 330013
  • Received:2019-03-27 Revised:2019-05-12 Online:2019-08-25 Published:2019-06-06
  • Contact: 10.6023/cjoc201903064 E-mail:he1208@mail.ccnu.edu.cn
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21877047, 21867011) and the Project of Science Fund of Jiangxi Education Office (No. GJJ170672).

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