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

Abstract

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.

Bioengineering functional copolymers: V. Synthesis, LCST, and thermal behavior of poly(N‐isopropyl acrylamide‐co‐p‐vinylphenylboronic acid)

“…Some aminoboron compounds have also found some utility in BNCT14 and other forms of cancer therapy;15 as a result, much effort has focused on the synthesis of boron‐containing amino acid and peptide derivatives for possible applications as enzyme inhibitors 16. Boronic acids, RB(OH) 2 , and boronate esters have received considerable attention as glucose sensors for diabetes therapy 17.…”

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“…14 Intracellular retention of sodium borocaptate in tumours was enhanced by use of electroporation. 15 Carborane conjugates with glycosides have been constructed, in which the glycoside moiety confers reduced toxicity and allows incorporation of DOI: 10.1039/b103007h fluorine label so that the uptake in cells can be monitored by 19 F NMR. 16 13 C NMR has been used to determine the structure of a conjugate of boronophenylalanine with fructose, under evaluation for BNCT treatment of melanoma, confirming that the boron is tetrahedral and anionic.…”

“…17 Not only the amount of boron deposited, but the microscopic localisation of boron within the target tissue (as demonstrated by ion microscopy) has been shown to influence the response to BNCT. 18 The chemotoxicity of boron compounds has been of interest both against tumour cells (trifluoromethylboron 19 ) and microorganisms (diolate complexes of boron with benzothiazoline co-ligands 20 ). A series of boron-containing peptide analogues has been evaluated as active-site-binding thrombin inhibitors.…”