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Mechanism-based design, synthesis and biological studies of N⁵-substituted tetrahydrofolate analogs as inhibitors of cobalamin-dependent methionine synthase and potential anticancer agents.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2012 Dec; Vol. 58, pp. 228-36. Date of Electronic Publication: 2012 Oct 09. - Publication Year :
- 2012
-
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.<br /> (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)
- Subjects :
- 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase metabolism
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Cell Death drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Enzyme Inhibitors chemical synthesis
Enzyme Inhibitors chemistry
HeLa Cells
Humans
Models, Molecular
Molecular Structure
Structure-Activity Relationship
Tetrahydrofolate Dehydrogenase metabolism
Tetrahydrofolates chemical synthesis
Tetrahydrofolates chemistry
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase antagonists & inhibitors
Antineoplastic Agents pharmacology
Drug Design
Enzyme Inhibitors pharmacology
Tetrahydrofolates pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 58
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 23124219
- Full Text :
- https://doi.org/10.1016/j.ejmech.2012.09.027