2. Academic Validation
  3. Mechanism-based design, synthesis and biological studies of N⁵-substituted tetrahydrofolate analogs as inhibitors of cobalamin-dependent methionine synthase and potential anticancer agents

Mechanism-based design, synthesis and biological studies of N⁵-substituted tetrahydrofolate analogs as inhibitors of cobalamin-dependent methionine synthase and potential anticancer agents

  • Eur J Med Chem. 2012 Dec:58:228-36. doi: 10.1016/j.ejmech.2012.09.027.
Zhili Zhang 1,  Chao Tian,  Shouxin Zhou,  Wei Wang,  Ying Guo,  Jie Xia,  Zhenming Liu,  Biao Wang,  Xiaowei Wang,  Bernard T Golding,  Roger J Griff,  Yansheng Du,  Junyi Liu
Affiliations

Affiliation

  • 1 Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
PMID: 23124219 DOI: 10.1016/j.ejmech.2012.09.027
Abstract

A number of 8-deazatetrahydrofolates bearing electrophilic groups on N(5) were designed and synthesized based on the action mechanism of methionine synthase, and their biological activities were investigated as well. Compounds (11b, 12b and 16) showed the most active against methionine synthase (IC(50): 8.11 μM, 1.73 μM, 1.43 μM). In addition, the cytotoxicity to human tumor cell lines and dihydrofolate reductase (DHFR) inhibition by target compounds were evaluated.

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