The cytotoxicity of trifluoromethyl boron derivatives and mode of action in human Tmolt3 T leukemic cells

Trifluoromethylboron derivatives proved to be cytotoxic in a number of murine and human leukemic and lymphoma screens. Solid tumor growth, e.g. glioma HS 683, breast Mck-7 and colon adenocarcinoma SW480, was reduced significantly by the compounds. Human Tmolt3 T-cell leukemia DNA synthesis was inhibited preferentially by the derivatives, with marginal effects on RNA and protein syntheses, after 60 min at 100 µM. The agents appeared to act by multiple mechanisms in that they inhibited the activities of DNA polymerase α, dihydrofolate reductase and nucleosides, significantly within 60 min at 100 µM. Deoxyribonucleotide pools were reduced after 60 min incubation with the compounds. Tmolt3 DNA fragmentation and reduced ct-DNA viscosity were evident after 24 h of incubation at 100 µM. ct-DNA thermal denaturation studies indicated that the agents caused some type of interaction with the bases of DNA. Copyright © 2000 John Wiley & Sons, Ltd.