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

Zhili Zhang, 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

Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

European journal of medicinal chemistry 2012 Dec

filter terms:

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. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Citation

Zhili Zhang, 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. Mechanism-based design, synthesis and biological studies of N⁵-substituted tetrahydrofolate analogs as inhibitors of cobalamin-dependent methionine synthase and potential anticancer agents. European journal of medicinal chemistry. 2012 Dec;58:228-36