Styrene is one of the most important industrial intermediates consumed in

Styrene is one of the most important industrial intermediates consumed in the world and is mainly used as a monomer for reinforced plastics and rubber. for the SAR study. Cytotoxicity of styrene and the halogenated styrene derivatives with an order of 4-bromostyrene > 4-chlorostyrene > 4-fluorostyrene ≈ styrene was observed in CYP2E1 transgenic cells. Comparable CD86 orders in the efficiency of the metabolism of styrene and the halogenated styrene analogues to their oxides and in the electrophilicity of the corresponding oxides were observed. Additionally the order of the potency of cellular glutathione depletion and the degree of proteins adduction induced by styrene as well as the halogenated styrenes had been in keeping with that of their cytotoxicities. The wild-type cells had been less vunerable to the toxicity from the matching model substances than CYP2E1 cells. Today’s study provided insight in to the roles from the chemical and biochemical properties of styrene in its cytotoxicity. = 8.4 and 11.5 Hz 1 CH2) 3.74 (dd = 3.4 and 11.5 Hz 1 CH2) 4.81 (dd = 3.4 and 8.4 Hz 1 CH) 7.52 (m 5 Ar). 4-Fluorostyrene glycol (10): 1H-NMR (300 MHz CDCl3) δ 3.36-2.68 (br 2 OH) 3.65 (dd = 8.3 and 11.4 Hz 1 CH2) 3.75 (dd = 3.4 and 11.4 Hz 1 CH2) 4.82 (dd = 3.4 and 8.3 Hz 1 CH) 7.07 = 2 and 8.5 Hz 2 Ar) 7.35 (dd = 5.4 and 8.5 Hz 2 Ar). 4-Chlorostyrene glycol (11): 1H-NMR (300 MHz CDCl3) δ 3.22-2.62 (br 2 MK-0518 OH) 3.64 (dd = 8.2 and 11.2 Hz 1 CH2) 3.76 (dd = 3.2 and 11.2 Hz 1 CH2) 4.82 (dd = 3.2 and 8.2 Hz 1 MK-0518 CH) 7.32 = 8.4 Hz 2 Ar) 7.36 (d MK-0518 = 8.4 Hz 2 Ar). 4-Bromostyrene glycol (12): 1H-NMR (300 MHz CDCl3) δ 3.32-2.74 (br 2 OH) 3.63 (dd = 8.2 and 11.4 Hz 1 CH2) 3.77 (dd = 3.4 and 11.4 Hz 1 CH2) 4.81 (dd = 3.4 and 8.2 Hz 1 CH) 7.27 = 8.4 Hz 2 Ar) 7.51 (d = 8.4 Hz 2 Ar). 2.3 Synthesis of styrene 4 4 and 4-bromostyrene oxide-derived cysteamine adducts (13-20) General procedure: the oxides (5 mmol) had been individually blended with cysteamine (7.5 mmol) in 10 mL of acetonitrile-water solution (6 : 1) containing triethylamine (10 mmol). The mixtures had been stirred at area heat range under an atmosphere of nitrogen for 36 h. The causing reaction mixtures had been diluted with ethyl acetate (30 mL) and washed with drinking water (10 mL × 3). The organic levels had been combined dried out over anhydrous Na2Thus4 and evaporated under vacuum. The residues had been put through column chromatography on silica gel to cover the next cysteamine adducts. The result of styrene oxide with cysteamine provided an assortment of 2-(2-aminoethylthio)-2-phenylethanol and 2-(2-aminoethylthio)-1-phenylethanol (13 and 17 approximate 1:1) as light yellowish essential oil (197 mg 20 in produce). MK-0518 1H-NMR (300 MHz CDCl3): δ 2.48-3.04 (m 6 + 8H) 3.8 (m 2 3.96 (dd = 5.7 7.9 1 4.78 (dd = 3.6 9 1 5.29 (brs 2 7.2 (m 5 × 2); = 198.2 [M+H]+. The result of 4-fluorostyrene oxide with cysteamine provided an assortment of 2-(2-aminoethylthio)-2-(4-fluorophenyl)ethanol and 2-(2-aminoethylthio)-1-(4-fluorophenyl)ethanol (14 and 18 approximate 1:1) as light yellowish essential oil (194 mg 18 1 (300 MHz CDCl3): δ 2.45-3.05 (m 6 + 8H) 3.78 (m 2 3.95 (dd = 6 7.2 1 4.78 (dd = 3.48 8.9 1 5.3 (brs 2 6.94 (m 2 × 2) 7.24 (m 2 × 2); = MK-0518 216.3 [M+H]+. The result of 4-chlorostyrene oxide with cysteamine provided an assortment of 2-(2-aminoethylthio)-2-(4-chloroophenyl)ethanol and 2-(2-aminoethylthio)-1-(4-chlorophenyl)ethanol (15 and 19 approximate 1:1) as light yellowish essential oil MK-0518 (150 mg 13 in produce). 1H-NMR (300 MHz CDCl3): δ 2.50-3.16 (m 6 + 8H) 3.72 (m 2 4.12 (dd = 7.1 14 1 4.78 (dd = 3.4 8.8 1 5.3 (brs 2 7.18 (m 4 × 2); = 232.1 [M+H]+. The result of 4-bromostyrene oxide with cysteamine provided an assortment of 2-(2-aminoethylthio)-2-(4-bromophenyl)ethanol and 2-(2-aminoethylthio)-1-(4-bromophenyl)ethanol (16 and 20 approximate 1:1) as light yellowish oil (206 mg 16 in yield). 1H-NMR (300 MHz CDCl3): δ 2.50-3.00 (m 6 + 8H) 3.79 (m 2 3.92 (dd = 5.6 7.6 1 4.75 (dd = 3.5 9 1 5.3 (brs 2 7.14 (m 2 × 2) 7.4 (m 2 × 2); = 276.0 [M+H]+. 2.4 Instrumentation The HPLC system contains an Agilent 1100 LC binary pump program and an Agilent 1100 Autosampler (Palo Alto CA). The HPLC program was interfaced having a PE Sciex API 2000 LC/MS/MS Program including an electrospray.