論文

Focusing on 2,2′-pyridoin (1, 1,2-di(2-pyridyl)-1,2-ethenediol) and its synthetic derivatives as the lead compound of the potent antioxidative enediol, their protective effect against oxidative stress was evaluated on the HL-60 cell system. 2,2′-Pyridoins showed no remarkable cytotoxic effect on HL-60 cells. The derivatives 1, 2, 3, 5, and 6 inhibited H2O2-induced cell death and intracellular oxidative stress more significantly than ascorbic acid. Since 2,2′-pyridoins are oxidized to the diketones, 2,2′-pyridils, in a protic solvent, the antioxidant activity of 2,2′-pyridils was also investigated. 2,2′-Pyridils showed antioxidant activity in the cell; however, the activity was lower than that of 2,2′-pyridoins. These results suggested that 2,2′-pyrdoin derivatives can be good cytoprotective agents against oxidative stress. © 2008 Elsevier Ltd. All rights reserved.

Various kinds of field-effect transistor (FET) have been fabricated with C60 nanowhisker (NW) and also studied for nanoelectronics application. Especially, pure and solvated C60 NWs have been synthesized in N2 environment so as to clarify the best device performance of C60 NW-FET. The FET works not only under vacuum but also in N2 environment when kept in the solvated condition. The solvated C60 NW-FET shows a clear improvement of their on/off ratio in the solvated condition, and the highest electron mobility after annealing. Although further study is needed, our results demonstrate the possibility, by appropriate choice of the solvent, of achieving good improvements in FET performance. Moreover, new kinds of C60 NW, such as derivative-based and nanotube-type one, have also been studied with regards to their fundamental FET characteristics. © 2008 The Japan Society of Applied Physics.

Crystalline precipitates composed of C60 and C 60(6,7-dimethoxytetralin) were prepared by the liquid-liquid interfacial precipitation method and examined by Raman spectroscopy and transmission electron microscopy (TEM). The as-prepared C60 nanotubes (C60NTs) dried in air exhibited a Raman spectrum showing a linearly polymerized structure, and a part of them turned to van der Waals polymers after drying in air. On the other hand, the C60NTs dried in air turned to a polymerized structure by irradiation of UV light. The whiskers prepared by use of C60 (6,7- dimethoxytetralin) showed an Ag(2) peak of 1460 cm-1 suggesting a polymerization of C60 and a Raman spectrum with sharp and clearly splitted peaks in the range of 200-800 cm -1, indicating a good crystallinity.

Nonylphenol, which is used industrially as a surfactant, is an endocrine-disrupting chemical (EDC) which has estrogenic activity. The novel biotransformation of nonylphenol was investigated, based on our previously reported ipso-metabolism of para-substituted phenols by cytochrome P450 (P450). Three novel metabolites of nonylphenol, i.e., nonylquinol, 4′- hydroxynonanophenone (CO-NP) as benzyl-oxidized nonylphenol, and hydroquinone, were detected in a rat liver microsome reaction mixture. On the other hand, production of 1-(4′-hydroxyphenyl)nonan-1-ol (OH-NP), namely benzyl-hydroxylated nonylphenol, was detected in a human liver microsome reaction mixture. The formation of all these metabolites was suppressed by the addition of P450 inhibitor. This showed that all nonylphenol metabolism was catalyzed by P450. To identify which P450 isoenzyme is involved in each reaction, fourteen human P450 (CYP) isozymes, CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, 3A7, and CYP4A11, were examined. CYP1A1, 1A2, and CYP2B6 effectively catalyzed the production of nonylquinol. CYP2B6 also catalyzed the benzyl-hydroxylation to give OH-NP. Hydroquinone was formed mainly from OH-NP, not via CO-NP. We examined the estrogenic activity of these new metabolites by estrogen receptor (ER)-binding reporter gene assay. Nonylquinol, OH-NP and hydroquinone have no ER-binding activity. However, CO-NP showed the same level of estrogen receptor binding activity as nonylphenol. Moreover, the amount of CONP formed was small. Therefore, the novel metabolic pathways led overall to metabolic inactivation, as concerns the estrogenic activity of nonylphenol through the ER.

Structural properties of various kinds of room-temperature synthesized C60 fullerene nanowhiskers were investigated by TEM and XRD. The C60 nanowhiskers prepared by use of toluene lost their initial solvated hexagonal structure faster than the C60 nanowhiskers prepared by use of m-xylene. The hexagonal structure of C60 nanowhiskers prepared by use of toluene was stabilized by adding C 60[C(COOC2H5)2]. These results suggest that large solute molecules in the C60 nanowhisker matrix stabilize their initially solvated hexagonal structure. Furthermore, the addition of a sufficient amount of C60(2-methoxycarbonyl-N- methylpyrrolidine) into the m-xylene solution of C60 produced the C60 nanowhiskers indicating the formation of ordered solid solution of C60 and C60(2-methoxycarbonyl-N-methylpyrrolidine).

Primary effusion lymphoma (PEL) is a subtype of non-Hodgkin's B-cell lymphoma and is an aggressive neoplasm caused by Kaposi's sarcoma-associated herpesvirus (KSHV) in immunosuppressed patients. In general, PEL cells are derived from post-germinal center B-cells and are infected with KSHV. To evaluate potential novel anti-tumor compounds against KSHV-associated PEL, seven water-soluble fullerene derivatives were evaluated as potential drug candidates for the treatment of PEL. Herein, we discovered a pyrrolidinium fullerene derivative, 1,1,1′,1′-tetramethyl [60]fullerenodipyrrolidinium diiodide, which induced apoptosis of PEL cells via a novel mechanism, the caspase-9 activation by suppressing the caspase-9 phosphorylation, causing caspase-9 inactivation. Pyrrolidinium fullerene treatment reduced significantly the viability of PEL cells compared with KSHV-uninfected lymphoma cells, and induced the apoptosis of PEL cells by activating caspase-9 via procaspase-9 cleavage. Pyrrolidinium fullerene additionally reduced the Ser473 phosphorylation of Akt and Ser196 of procaspase-9. Ser473-phosphorylated Akt (i.e., activated Akt) phosphorylates Ser196 in procaspase-9, causing inactivation of procaspase-9. We also demonstrated that Akt inhibitors suppressed the proliferation of PEL cells compared with KSHV-uninfected cells. Our data therefore suggest that Akt activation is essential for cell survival in PEL and a pyrrolidinium fullerene derivative induced apoptosis by activating caspase-9 via suppression of Akt in PEL cells. In addition, we evaluated whether pyrrolidinium fullerene in combination with the HSP90 inhibitor (geldanamycin; GA) or valproate, potentiated the cytotoxic effects on PEL cells. Compared to treatment with pyrrolidinium fullerene alone, the addition of low-concentration GA or valproate enhanced the cytotoxic activity of pyrrolidinium fullerene. These results indicate that pyrrolidinium fullerene could be used as a novel therapy for the treatment of PEL. © 2014 Elsevier Inc. All rights reserved.

We have already reported that the quinol formation from some para- alkylphenols, which is a novel metabolic pathway catalyzed by cytochrome P- 450, occurs in a rat liver microsomal system (Ohe et al., 1997). In the present study, we investigated whether estrone and 17β-estadiol, each of which contains a p-alkylphenol moiety, are also oxidized into the corresponding quinols by cytochrome P-450. Six recombinant human cytochrome P-450 enzymes, CYP1A1, CYP1A2, CYP2B6, CYP2C9, CYP2E1, and CYP3A4, were tested. The results show that estrone and 17β-estadiol were converted into the corresponding quinols by CYP1A1, CYP2B6, and CYP2E1.