Premium
Synthesis and Cytotoxic Action of 1‐Oxoalkyl and 1,2‐Dioxoalkyl‐1,2,4‐triazolidine‐3,5‐diones in Murine and Human Tissue Cultured Cells
Author(s) -
MacLauchlin Christopher,
Hall Iris H.,
Izydore Robert A.
Publication year - 1999
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/(sici)1521-4184(19997)332:7<225::aid-ardp225>3.0.co;2-2
Subject(s) - dihydrofolate reductase , cytotoxic t cell , thymidylate synthase , nucleoside , dna , chemistry , biochemistry , l1210 cells , nucleic acid , enzyme , dna synthesis , nucleic acid metabolism , microbiology and biotechnology , biology , rna , cytotoxicity , in vitro , cancer , gene , genetics , fluorouracil
1‐Oxoalkyl and 1,2‐dioxoalkyl‐1,2,4‐triazolidine‐3,5‐diones proved to be potent antineoplastic agents in mouse tumors and potent cytotoxic agents particularly against the growth of suspended tumor cells. The compounds with shorter substituents in position 1 or positions 1 and 2 afforded the better activity. In L1210 lymphoid leukemia cells DNA, RNA, and protein syntheses were inhibited at 100 μM after 60 min. Multiple enzyme sites in nucleic acid metabolism were affected by the compounds, i.e. DNA polymerase α, PRPP‐amido transferase, dihydrofolate reductase, thymidylate synthetase, and nucleoside kinases. These effects of the agents are probably additive in bringing about inhibition of DNA synthesis and cell death.