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Activity of the new antifolate N10-propargyl-5,8-dideazafolate and its polyglutamates against human dihydrofolate reductase, human thymidylate synthetase, and KB cells containing different levels of dihydrofolate reductase. 1985

Y C Cheng, and G E Dutschman, and M C Starnes, and M H Fisher, and N T Nanavathi, and M G Nair

The action of N10-propargyl-5,8-dideazafolate (PDDF) and its gamma-polyglutamyl analogues against human thymidylate synthetase and dihydrofolate reductase was examined. PDDF inhibited thymidylate synthetase in a noncompetitive fashion with respect to 5,10-methylenetetrahydrofolate and dihydrofolate reductase in a competitive fashion with respect to dihydrofolate. Ki values were estimated to be 20 and 250 nM, respectively. The addition of glutamyl moieties through gamma-linkage enhanced the inhibitory activity of PDDF against thymidylate synthetase without significant effect on dihydrofolate reductase. PDDF inhibited human KB cell growth, and its potency was found to be influenced less than that of methotrexate by the amount of cellular dihydrofolate reductase.

UI MeSH Term Description Entries
D007624 KB Cells This line KB is now known to be a subline of the ubiquitous KERATIN-forming tumor cell line HeLa. It was originally thought to be derived from an epidermal carcinoma of the mouth, but was subsequently found, based on isoenzyme analysis, HeLa marker chromosomes, and DNA fingerprinting, to have been established via contamination by HELA CELLS. The cells are positive for keratin by immunoperoxidase staining. KB cells have been reported to contain human papillomavirus18 (HPV-18) sequences. HeLa-KB Cells,Cell, HeLa-KB,Cell, KB,Cells, HeLa-KB,Cells, KB,HeLa KB Cells,HeLa-KB Cell,KB Cell
D007780 Lacticaseibacillus casei A rod-shaped bacterium isolated from milk and cheese, dairy products and dairy environments, sour dough, cow dung, silage, and human mouth, human intestinal contents and stools, and the human vagina. L. casei is CATALASE positive. Lactobacillus casei
D007939 Leukemia L1210 An experimental LYMPHOCYTIC LEUKEMIA of mice. Leukemia L 1210,L 1210, Leukemia,L1210, Leukemia
D008433 Mathematics The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Mathematic
D008727 Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D008780 Methyltransferases A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1. Methyltransferase
D011624 Pteroylpolyglutamic Acids Derivatives of folic acid (pteroylglutamic acid). In gamma-glutamyl linkage they are found in many tissues. They are converted to folic acid by the action of pteroylpolyglutamate hydrolase or synthesized from folic acid by the action of folate polyglutamate synthetase. Synthetic pteroylpolyglutamic acids, which are in alpha-glutamyl linkage, are active in bacterial growth assays. Folate Polyglutamates,Polyglutamate Folates,Pteroylpolyglutamates,Acids, Pteroylpolyglutamic,Folates, Polyglutamate,Polyglutamates, Folate
D011799 Quinazolines A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring. Quinazoline
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug

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