Chin. J. Org. Chem. ›› 2012, Vol. 32 ›› Issue (10): 1944-1950.DOI: 10.6023/cjoc1203122 Previous Articles     Next Articles



周受辛a, 田超a, 郭莹a, 王孝伟a, 刘俊义a,b, 张志丽a   

  1. a 北京大学药学院化学生物学系 北京 100191;
    b 北京大学药学院 天然药物与仿生药物国家重点实验室 北京 100191
  • 收稿日期:2012-03-12 修回日期:2012-05-11 发布日期:2012-06-04
  • 通讯作者: 张志丽
  • 基金资助:

    国家自然科学基金(Nos. 21042009, 21172014)和国家科技部(No. 2009ZX09301-010)资助项目.

Synthesis and Bioactivity of 8-Deaza Folic Acid Analogues of Thiophene

Zhou Shouxina, Tian Chaoa, Guo Yinga, Wang Xiaoweia, Liu Junyia,b, Zhang Zhili a   

  1. a Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191;
    b State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191
  • Received:2012-03-12 Revised:2012-05-11 Published:2012-06-04
  • Supported by:

    Project supported by the National Science Foundation of China (Nos. 21042009, 21172014) and the Ministry of Science and Technology of China (No. 2009ZX09301-010).

Based on the action mechanism of methionine synthase and structures of inhibitors against dihydrofolic reductase, thiophene derivatives of 8-deaza folic acid were designed as dual-target inhibitors. Two target compounds were obtained by nitration, reduction, condensation, and hydrolysis with 2-thiophenecarboxylic acid as starting material, and were characterized by 1H NMR, 13C NMR and MS techniques. The inhibitory activities against methionine synthase and recombinant human dihydrofolate reductase were determined. The target compounds showed inhibitory activity on both two enzymes. The IC50s of one compound were 25.2 and 2.3 μmol/L against methionine synthase and recombinant human dihydrofolate reductase, respectively.

Key words: thiophene derivatives of 8-deaza folic acid, methionine synthase, dihydrofolate reductase, nitration, bioactivity