N-acetylcysteine blocks apoptosis induced by N-alpha-tosyl-L-phenylalanine chloromethyl ketone in transformed T-cells

The serine protease inhibitor N-alpha-tosyl-L-phenylalanine chloromethyl ketone (TPCK) can interfere with cell-cycle progression and has also been shown either to protect cells from apoptosis or to induce apoptosis. We tested the effect of TPCK on two transformed T-cell lines. Both Jurkat T-cells and Theileria parva-transformed T-cells were shown to be highly sensitive to TPCK-induced growth arrest and apoptosis. Surprisingly, we found that the thiol antioxidant, N-acetylcysteine (NAC), as well as L- or D-cysteine blocked TPCK-induced growth arrest and apoptosis. TPCK inhibited constitutive NF-kappaB activation in T. parva-transformed T-cells, with phosphorylation of IkappaBalpha and IkappaBbeta being inhibited with different kinetics. TPCK-mediated inhibition of IkappaB phosphorylation, NF-kappaB DNA binding and transcriptional activity were also prevented by NAC or cysteine. Our observations indicate that apoptosis and NF-kappaB inhibition induced by TPCK result from modifications of sulphydryl groups on proteins involved in regulating cell survival and the NF-kappaB activation pathway(s).

Synthesis of bis(3-{[2-(allyloxy)ethoxy]methyl}-2,4,6-trimethylbenzoyl)(phenyl)phosphine oxide - a tailor-made photoinitiator for dental adhesives

Because of the poor solubility of the commercially available bisacylphosphine oxides in dental acidic aqueous primer formulations, bis(3-{[2-(allyloxy)ethoxy]methyl}-2,4,6-trimethylbenzoyl)(phenyl)phosphine oxide (WBAPO) was synthesized starting from 3-(chloromethyl)-2,4,6-trimethylbenzoic acid by the dichlorophosphine route. The substituent was introduced by etherification with 2-(allyloxy)ethanol. In the second step, 3-{[2-(allyloxy)ethoxy]methyl}-2,4,6-trimethylbenzoic acid was chlorinated. The formed acid chloride showed an unexpected low thermal stability. Its thermal rearrangement at 180 ° C resulted in a fast formation of 3-(chloromethyl)-2,4,6-trimethylbenzoic acid 2-(allyloxy)ethyl ester. In the third step, the acid chloride was reacted with phenylphosphine dilithium with the formation of bis(3-{[2-(allyloxy)ethoxy]methyl}-2,4,6-trimethylbenzoyl)(phenyl)phosphine, which was oxidized to WBAPO. The structure of WBAPO was confirmed by ¹H NMR, ¹³C NMR, ³¹P NMR, and IR spectroscopy, as well as elemental analysis. WBAPO, a yellow liquid, possesses improved solubility in polar solvents and shows UV-vis absorption, and a high photoreactivity comparable with the commercially available bisacylphosphine oxides. A sufficient storage stability was found in dental acidic aqueous primer formulations.