Cytotoxicity of rhenium(I) alkoxo and hydroxo carbonyl complexes in murine and human tumor cells.
The rhenium(I) alkoxo/hydroxo carbonyl complexes were shown to be very potent in suspended tumor cell lines in suppressing growth but were more selective in inhibiting the growth of cultures from solid tumors. Their mode of action in L1210 lymphoid leukemia cells indicated that they were not alkylating agents but interfered with nucleic acid metabolism at multiple enzyme sites, e.g. dihydrofolate reductase, PRPP-amido transferase, thymidine kinase, with DNA strand scission after 60 min incubation. These compounds did not function mechanistically exclusively as cisplatin derivatives causing intrastrand linkages of DNA but rather they mimicked the metal complexes of aminecarboxyboranes, furan oximes, N-substituted thiosemicarbazones, trifluoromethyl borons and ferratricarbadecarbanyl complexes acting as antimetabolites.
Yan
Y K
YK
Division of Chemistry, Nanyang Technological University, Singapore.
Cho
S E
SE
Shaffer
K A
KA
Rowell
J E
JE
Barnes
B J
BJ
Hall
I H
IH
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007939:Leukemia L1210 / Q000378:metabolism; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D012211:Rhenium / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D019384:Nucleic Acid Synthesis Inhibitors; D009942:Organometallic Compounds; D012211:Rhenium; D004247:DNA