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Chinese Journal of Organic Chemistry >

2012 , Vol. 32 >Issue 10: 1944 - 1950

DOI: https://doi.org/10.6023/cjoc1203122

Articles

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

  • Zhou Shouxin ,
  • Tian Chao ,
  • Guo Ying ,
  • Wang Xiaowei ,
  • Liu Junyi ,
  • Zhang Zhili
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  • 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 date: 2012-03-12

  Revised date: 2012-05-11

  Online 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).

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Abstract

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

Cite this article

Zhou Shouxin , Tian Chao , Guo Ying , Wang Xiaowei , Liu Junyi , Zhang Zhili . Synthesis and Bioactivity of 8-Deaza Folic Acid Analogues of Thiophene[J]. Chinese Journal of Organic Chemistry, 2012 , 32(10) : 1944 -1950 . DOI: 10.6023/cjoc1203122

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