Fiammetta Ferroni

Cytotoxic and antioxidant activity of 4-methylthio-3-butenyl isothiocyanate from Raphanus sativus L. (Kaiware Daikon) sprouts.

There is high current interest in the chemopreventive potential of Brassica vegetables (cruciferae), particularly due to their content in glucosinolates (GL), which upon myrosinase hydrolysis release the corresponding isythiocyanates (ITC). Some ITCs, such as sulforaphane (SFN) from broccoli ( Brassica oleacea italica), have been found to possess anticancer activity through induction of apoptosis in selected cell lines, as well as indirect antioxidant activity through induction of phase II detoxifying enzymes. Japanese daikon ( Raphanus sativus L.) is possibly the vegetable with the highest per capita consumption within the Brassicaceae family. Thanks to a recently improved gram scale production process, it was possible to prepare sufficient amounts of the GL glucoraphasatin (GRH) as well as the corresponding ITC 4-methylthio-3-butenyl isothiocyanate (GRH-ITC) from its sprouts. This paper reports a study on the cytotoxic and apoptotic activities of GRH-ITC compared with the oxidized counterpart 4-methylsulfinyl-3-butenyl isothiocyanate (GRE-ITC) on three human colon carcinoma cell lines (LoVo, HCT-116, and HT-29) together with a detailed kinetic investigation of the direct antioxidant/radical scavenging ability of GRH and GRH-ITC. Both GRH-ITC and GRE-ITC reduced cell proliferation in a dose-dependent manner and induced apoptosis in the three cancer cell lines. The compounds significantly ( p < 0.05) increased Bax and decreased Bcl2 protein expression, as well as producing caspase-9 and PARP-1 cleavage after 3 days of exposure in the three cancer cell lines. GRH-ITC treatment was shown to have no toxicity with regard to normal human lymphocytes (-15 +/- 5%) in comparison with SFN (complete growth inhibition). GRH and GRH-ITC were able to quench the 2,2-diphenyl-1-picrylhydrazyl radical, with second-order rate constants of 14.0 +/- 2.8 and 43.1 +/- 9.5 M(-1) s(-1), respectively (at 298 K in methanol), whereas the corresponding value measured here for the reference antioxidant alpha-tocopherol was 425 +/- 40 M (-1) s (-1). GRH reacted with H2O2 and tert-butyl hydroperoxide in water (pH 7.4) at 37 degrees C, with rate constants of 1.9 +/- 0.3 x 10(-2) and 9.5 +/- 0.3 x 10(-4) M(-1) s (-1) (paralleling recently developed synthetic antioxidants) being quantitatively (>97%) converted to GRE. It is demonstrated that GRH-ITC has interesting antioxidant/radical scavenging properties, associated with a selective cytotoxic/apoptotic activity toward three human colon carcinoma cell lines, and very limited toxicity on normal human T-lymphocytes.

Effective cholesteric liquid crystal inducers based on axially chiral alleno-acetylenes

Axially chiral alleno-acetylenes, modified with lateral aryl groups via short and convenient synthetic pathways, are presented as efficient chiral dopants for producing cholesteric liquid crystals.

Kinetics of the enolisation reaction of 2-acetylfuran, 2-acetyl-N-methylpyrrole and 3-acetyl-N-methylpyrrole

Kinetic results are reported on the rates of enolisation of 2-acetylfuran, 2-acetyl-N-methylpyrrole and 3-acetyl-N-methylpyrrole in water, in buffer, in dilute hydrochloric acid solutions, in dilute sodium hydroxide solutions and in the presence of several metal ion salts, as measured by their rates of halogenation. The results have been compared with those of corresponding reactions of 2-acetylthiophene, 3-acetylthiophene and acetophenone. In metal ion promoted reactions the catalytic effects observed are probably due to coordination of the carbonyl oxygen in the reaction transition states, while there is no evidence of participation of the heteroatoms of the aromatic rings in chelation. Metal activating factors are particularly high for the acetylpyrroles where, for example, Cu2+ is up to 740 times more effective than the proton in catalysing the enolisation reaction of 3-acetyl-N-methylpyrrole. This is in agreement with the high negative charge density on the oxygen atom recently observed by NMR spectroscopy for the acetylpyrroles as compared to acetylfurans, acetylthiophenes and acetophenone.

A 13C n.m.r. study of 5-cyano-, 5-methoxycarbonyl-, 5-carbamoyl-, and 5-acetyl-3-nitro-2-X-thiophenes: substituent effects and their relation to the charge distribution in corresponding 2,2-dimethoxy Meisenheimer adducts

A 13C n.m.r. study in (CD3)2SO has been carried out on 5-cyano-(5), 5-methoxycarbonyl-(6), 5-carbamoyl-(7), and 5-acetyl-3-nitro-2-X-thiophenes (8) in order to investigate the 2-X-substituent effect on the C(α) chemical shifts of the different 5-probes. The results obtained show that, unlike the case of the acetyl group, the α-carbon chemical shifts of the cyano, methoxycarbonyl, and carbamoyl groups are not appreciably affected by through-conjugation with the 2-X-substituents, π-polarization being the more important outcome of the substituent effect on the probe group. The analysis of both the C(5) and C(α) chemical-shift variations in the series (5)–(8), by means of a gradual modification of the electron-releasing power of the substituents, reveals a trend which has been interpreted as a useful indicator of the electronic effects in play on the distribution of the π-electron densities in the corresponding Meisenheimer adducts (1)–(4).