Chemical Research in Chinese Universities ›› 2015, Vol. 31 ›› Issue (5): 742-745.doi: 10.1007/s40242-015-5194-z

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Design, Synthesis and Activities of Aziridine Derivatives of N5-Methyltetrahydrofolate Against Methionine Synthase

DENG Xiling1,3, GUO Ying1, TIAN Chao1, LIU Junyi1,2, WANG Xiaowei1, ZHANG Zhili1   

  1. 1. School of Pharmaceutical Sciences, Peking University, Beijing 100191, P. R. China;
    2. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, P. R. China;
    3. School of Pharmaceutical Sciences, Shihezi University, Shihezi 832000, P. R. China
  • Received:2015-05-14 Revised:2015-07-20 Online:2015-10-01 Published:2015-07-22
  • Contact: ZHANG Zhili, E-mail: lilybmu@bjmu.edu.cn E-mail:lilybmu@bjmu.edu.cn
  • Supported by:

    Supported by the National Natural Science Foundation of China(No.21172014).

Abstract:

Aziridine derivatives of N5-methyltetrahydrofolate were designed and synthesized based on the mechanism of methionine synthase, and their biological activities were investigated as well. The aziridine derivatives 1 and 6 exhibited superior inhibitory activities(IC50: 5.05 and 4.15 μmol/L, respectively) compared to the corresponding chain analogue 4(IC50=24.42 μmol/L). The results suggest that the aziridine derivatives can get potential activities against nucleophilic methionine synthase.

Key words: Aziridine, Methionine synthase, Ring closure reaction, N5-Methyltetrahydrofolate