Mechanism-based design, synthesis and biological studies of N 5-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

Research output: Contribution to journalArticle

13 Scopus citations

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 (IC50: 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.

Original languageEnglish (US)
Pages (from-to)228-236
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume58
DOIs
StatePublished - Dec 1 2012

Keywords

  • 8-Deazatetrahydrofolates
  • Antitumor
  • Folate inhibitor
  • Methionine synthase

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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