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Cytotoxicity of Metallic Complexes of Furan Oximes in Murine and Human Tissue Cultured Cell Lines
Author(s) -
Hall Iris H.,
Lee Christian C.,
Ibrahim Ghassan,
Khan Mustayeen A.,
Bouet Gilles M.
Publication year - 1997
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/(sici)1099-0739(199707)11:7<565::aid-aoc608>3.0.co;2-i
Subject(s) - chemistry , cytotoxicity , topoisomerase , ribonucleoside , dna , purine , nucleoside , pyrimidine , cell culture , apoptosis , programmed cell death , cytotoxic t cell , biochemistry , microbiology and biotechnology , l1210 cells , stereochemistry , enzyme , rna , in vitro , biology , genetics , gene
The copper complexes of furan oxime derivatives were found to be potent cytotoxic agents in both murine and human tissue cultured cell lines which were suspended as well as solid tumors. Mode of action studies in murine L1210 lymphoid leukemia cells showed that the compounds suppressed DNA, RNA and protein synthesis after 60 min at 100 μM. Inhibition of purine and pyrimidine de novo syntheses, as well as inhibition of ribonucleoside reductase and nucleoside kinase activities with DNA strand scission occurred. All of these effects of the drug probably added to its ability to cause cell death but most important was the inhibition of DNA topoisomerase II activity with IC 50 values lower than those afforded by VP‐16, the standard, which should cause apoptosis. © 1997 John Wiley & Sons, Ltd.