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101.
Malliga R. Iyer Yong Sok Lee Jeffrey R. Deschamps Richard B. Rothman Christina M. Dersch Arthur E. Jacobson Kenner C. Rice 《Bioorganic & medicinal chemistry》2010,18(1):91-99
A series of N-substituted rac-cis-4a-ethyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-8-ols have been prepared using a simple synthetic route previously designed for synthesis of related cis-2-methyl-4a-alkyl-1,2,3,4,4a,9a-hexahydrobenzofuro[2,3-c]pyridin-6-ols. The new phenolic compounds, where the aromatic hydroxy moiety is situated ortho to the oxygen atom in the oxide-bridged ring, do not interact as well as the pyridin-6-ols with opioid receptors. The N-para-fluorophenethyl derivative had the highest μ-opioid receptor affinity of the examined compounds (Ki = 0.35 μM). 相似文献
102.
103.
Choi YA Park JS Park MY Oh KS Lee MS Lim JS Kim KI Kim KY Kwon J Yoon do Y Moon EY Yang Y 《FEBS letters》2011,(5):755-760
The cancerous inhibitor of protein phosphatase 2A (CIP2A) increases the migration and metastasis of various cancer cells. Overexpression of CIP2A has been shown to increase the proliferation of MDA-MB-231 cells. We thus assessed whether CIP2A expression is associated with sensitivity to doxorubicin. MDA-MB-231 cells showed an increase in CIP2A expression after treatment with doxorubicin, while MCF-7 cells showed a decrease in CIP2A expression. The overexpression of CIP2A in MCF-7 cells overcame the inhibition of cell proliferation in response to doxorubicin treatment. CIP2A expression was not affected by wild-type or mutant p53. However, mutant p53 blocked doxorubicin-mediated CIP2A down-regulation in HCT116 cells. As a regulation mechanism of doxorubicin-mediated CIP2A expression, we showed that phosphorylated Akt was involved in the suppression of CIP2A expression. 相似文献
104.
Manning DD Cioffi CL Usyatinsky A Fitzpatrick K Masih L Guo C Zhang Z Choo SH Sikkander MI Ryan KN Naginskaya J Hassler C Dobritsa S Wierschke JD Earley WG Butler AS Brady CA Barnes NM Cohen ML Guzzo PR 《Bioorganic & medicinal chemistry letters》2011,21(1):58-61
Serotonin type 3 (5-HT3) receptor partial agonists are being targeted as potential new drugs for the treatment of irritable bowel syndrome (IBS). Two new chemical series bearing indazole and indole cores have exhibited nanomolar binding affinity for the h5-HT3A receptor. A range of partial agonist activities in HEK cells heterologously expressing the h5-HT3A receptor were measured for the indazole series. Excellent 5-HT3 receptor selectivity, favorable in vitro metabolic stability and CYP inhibition properties, and good oral in vivo potency in the murine von Bezold-Jarisch reflex model is exemplified thereby indicating the series to have potential utility as improved IBS agents. 相似文献
105.
106.
Hao P Qian J Dutta B Cheow ES Sim KH Meng W Adav SS Alpert A Sze SK 《Journal of proteome research》2012,11(3):1804-1811
Deamidation of asparaginyl residues in proteins produces a mixture of asparaginyl, n-aspartyl, and isoaspartyl residues, which affects the proteins' structure, function, and stability. Thus, it is important to identify and quantify the products to evaluate the effects in biological systems. It is still a challenging task to distinguish between the n-Asp and isoAsp deamidation products in a proteome-wide analysis because of their similar physicochemical properties. The quantification of the isomeric deamidated peptides is also rather difficult because of their coelution/poor separation in reverse-phase liquid chromatography (RPLC). We here propose a RP-ERLIC-MS/MS approach for separating and quantifying on a proteome-wide scale the three products related to deamidation of the same peptide. The key to the method is the use of RPLC in the first dimensional separation and ERLIC (electrostatic repulsion-hydrophilic interaction chromatography) in the second, with direct online coupling to tandem MS. The coelution of the three deamidation-related peptides in RPLC is then an asset, as they are collected in the same fraction. They are then separated and identified in the second dimension with ERLIC, which separates peptides on the basis of both pI and GRAVY values. The coelution of the three products in RPLC and their efficient separation in ERLIC were validated using synthetic peptides, and the performance of ERLIC-MS/MS was tested using peptide mixtures from two proteins. Applying this sequence to rat liver tissue, we identified 302 unique N-deamidated peptides, of which 20 were identified via all three deamidation-related products and 70 of which were identified via two of them. 相似文献
107.
The preincubation of potato lipoxygenase with 9(S)-hydroperoxyoctadecatrienoic acid, 15(S)-hydroperoxyeicosatetraenoic acid or 5(S)-hydroperoxyeicosatetraenoic acid which can be subjected to further lipoxygenation led to the gradual inactivation of the lipoxygenase activity, whereas 13(S)-hydroperoxy-9,13,15-octadecatrienoic acid or 15(S)-hydroperoxy-11,13,17-eicosatrienoic acid had no significant effect. The inhibitory effect of the peroxy acids was abolished by hemoglobin. Based on these observations, it is proposed that the unstable epoxide intermediates from the respective peroxy acids may be responsible for the inactivation of potato lipoxygenase. In the comparative study, it was found that 15(S)-hydroperoxyeicosatetraenoic acid possessed more effective inhibitory role than the other acids with Ki value of 250 microM. 相似文献
108.
Michaŀ Kozakiewicz Agnieszka Choŀuj Anna Kozakiewicz Miŀosŀawa Sokóŀ 《Acta theriologica》2009,54(2):157-164
A laboratory experiment was carried out in order to test the hypothesis that in a free-living population of bank volesMyodes glareolus Schreber, 1740, long distance movements and mating with females representing other breeding colonies may be a male strategy
to increase their reproductive success. In an experimental cage system, the behaviour of female bank voles towards males that
were either familiar to them or strangers was investigated, including whether or not females will accept stranger males as
breeding partners. It was found that females did not display increased aggression towards stranger males; instead they tried
to contact them and the level of female interaction did not differ significantly between the two categories of males. Based
on an analysis of microsatellite markers in the genomic DNA of adults and their young, the proportion of offspring fathered
by the stranger and familiar males was the same. In addition, a considerable proportion (40%) of double paternity litters
was found among those obtained during the course of the study. 相似文献
109.
H.S. Cui L.S. Huang D.-E. Sok J. Shin B.-M. Kwon U.J. Youn K. Bae 《Phytomedicine》2007,14(10):696-700
Neuroprotective effect of honokiol (HK), orally administered, on oxidative damage in the brain of mice challenged with N-methyl-d-aspartic acid (NMDA) was examined. HK (1-100 mg/kg) was administered to Institute of Cancer Research (ICR) male mice through a gavage for 3 days consecutively, and on the third day, NMDA (150 mg/kg) was intraperitoneally (i.p.) administered. Administration of NMDA, causing a lethality of approximately 60%, resulted in a significant decrease of total glutathione (GSH) level and increase of thiobarbituric acid-reactive substances (TBARS) value in brain tissue. Meanwhile, oral administration of HK (> or = 3 mg/kg) for 3 days reduced the lethality (60%) in NMDA-treated group to 10% level, and alleviated the behavioral signs of NMDA neurotoxicity. Moreover, HK pretreatment restored the levels of total GSH and TBARS in the brain tissue to control levels (p<0.01). Additionally, GSH peroxidase activity in cytosolic portion of brain homogenate was also restored significantly (p<0.01), whereas GSH reductase activity was not. Separately, compared to vehicle-treated control, no significant changes in body and brain weight were observed in mice administered with HK. Based on these results, oral intake of HK is suggested to prevent oxidative stress in the brain of mice. 相似文献
110.
While incubation of soybean lipoxygenase with alpha-linolenic acid resulted in the gradual decrease of lipoxygenase activity, the incubation with linoleic acid had no change. The inactivation of soybean lipoxygenase during incubation with alpha-linolenic acid was markedly observed at pH 6.5, but not at pH 9.0. Among the lipoxygenation products of alpha-linolenic acid, only 9(S)-hydroperoxyoctadecatrienoic acid caused the inactivation of lipoxygenase. 9(S)-Hydroxyoctadecatrienoic acid, 13(S)-hydroperoxyoctadecatrienoic acid or 9,16-dihydroperoxy conjugated trienoic acid was without effect. Accordingly, it is suggested that the epoxide intermediate, one conversion product of 9(S)-hydroperoxyoctadecatrienoic acid, might be involved in the direct inactivation of lipoxygenase. 相似文献