The cytotoxicity of trifluoromethyl boron derivatives and mode of action in human Tmolt(3) T leukemic cells

Trifluoromethylboron derivatives proved to be cytotoxic in a number of muri ne and human leukemic and lymphoma screens. Solid tumor growth, e.g. glioma HS 683, breast Mck-7 and colon adenocarcinoma SW480, was reduced significa ntly by the compounds, Human Tmolt(3) T-cell leukemia DNA synthesis was inh ibited preferentially by the derivatives, with marginal effects on RNA and protein syntheses, after 60 min at 100 mu M. The agents appeared to act by multiple mechanisms in that they inhibited the activities of DNA polymerase alpha, dihydrofolate reductase and nucleosides, significantly within 60 mi n at 100 mu M I. Deoxyribonucleotide pools were reduced after 60 min incuba tion with the compounds. Tmolt(3) DNA fragmentation and reduced ct-DNA visc osity were evident after 24 h of incubation at 100 mu M. ct-DNA thermal den aturation studies indicated that the agents caused some type of interaction with the bases of DNA, Copyright (C) 2000 John Wiley & Sons, Ltd.