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目的:为进一步揭示红花Carthamus tinctorius L.药理活性的化学物质基础,开发其活性成分,我们对其进行了较为深入系统的化学成分研究。方法;经大孔树脂,硅胶和Sephadex LH-20反复柱层分得并通过波波谱分析鉴定了12个化合物。结果:它们分别为2,3,4,9-tetrahydro-1-methyl-1-H-pyrido[3,4-b]indole-3-carboxylicacid(Ⅰ);thymine-2-desoxyribofuranoside(Ⅱ);ethyl-α-D-lyxofuranoside(Ⅲ);kaempferol-3-O-rutinoside(Ⅳ);syringin(Ⅴ);quercetin-3-O-β-D-galactoside(Ⅵ);safflor yellow-A(Ⅶ);carthamin(Ⅷ)和阿魏酸,对羟基玻酸,胡萝卜苷,β-谷甾醇。结论:化合物Ⅰ,Ⅱ和Ⅲ为首次从该植物中分得。化合物Ⅶ对ADP诱导的大鼠血小板聚集有较好的抑制活性。 相似文献
3.
Several amides of 3-(3,6-dioxo-2,4-dimethylcyclohexa-l,4-diene)-3,3-diniethylpropionic acid (2) have been synthesized and tested as model redox-sensitive pro-prodrugs of amines. The reduction of these model pro-prodrugs generated hydroxy amide intermediates 4a-4h, the lactonization of which resulted in amine release. The rates of lactonization of 4a-4h were investigated at pH 7.4 and 37°C. The half-lives for appearance of the product lactone la from these intermediates were found to range from 1.4 to 3.4 min. With such rapid lactonization rates, it is believed that reduction will be the rate-limiting step in the two-step conversion of the pro-prodrug to the amine. 相似文献
4.
Role of pharmacogenomics and pharmacodynamics in the treatment of acute lymphoblastic leukaemia 总被引:1,自引:0,他引:1
Pharmacodynamic studies have been used to establish the relationships between the administered dosage and the concentration of drugs and metabolites in the blood or tissues and that between these concentrations and pharmacological effects. Polymorphisms in the genes that encode drug-metabolizing enzymes, drug transporters and drug targets can affect a person's response to therapy and may affect the development of de novo or therapy-related leukaemias. The burgeoning field of pharmacogenomics elucidates inherited differences in drug metabolism and treatment response. Increasingly, pharmacodynamic and pharmacogenomic studies are being used to individualize therapy to enhance efficacy and reduce toxicity. 相似文献
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NRH:quinone reductase (QR2) is present in the retinas of embryonic and post-hatched (PH) chicks. 5-Methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) is a QR2 ligand that increases cAMP levels in developing retinas, but it does not affect cAMP levels in CHO-QR2 cells. The dopamine quinone reductase activity of QR2 retrieves dopamine, which increases cAMP levels in developing retinas. The objective of the present study was to investigate whether 5-MCA-NAT increases endogenous dopamine levels in retinas from chick embryos and post-hatched chicks. Endogenous dopamine was measured by enzyme-linked immunosorbent assay (ELISA). 5-MCA-NAT increased retinal endogenous dopamine levels at all developmental stages studied and in PH chicks (−log EC50 = 11.62 ± 0.34 M). This effect was inhibited by non-selective antagonists of receptors and melatonin binding sites N-acetyl-2-benzyltryptamine (luzindole, 5 μM), but it was not inhibited by the Mel1b melatonin receptor antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT, 10 nM). The QR2 cosubstrate, N-methyl-dihydronicotinamide (NMH) (−log EC50 = 6.74 ± 0.26 M), increased endogenous dopamine levels in controls and in retinas stimulated with 5-MCA-NAT (3 nM). The QR2 inhibitor benzo[e]pyrene inhibited endogenous dopamine levels in both control (−log IC50 = 7.4 ± 0.28 M) and NMH-stimulated (at 100 nM and 1 μM benzo[e]pyrene concentrations) retinas. Theoretical studies using Molegro Virtual Docking software corroborated these experimental results. We conclude that 5-MCA-NAT increases the level of endogenous dopamine via QR2. We suggest that this enzyme triggers double reduction of the dopamine quinone, recovering dopamine in retinal development. 相似文献
7.
《Pathology, research and practice》2020,216(11):153173
Pyruvate kinase M2 (PKM2) and NAD(P)H:quinone oxidoreductase-1 (NQO1) have been known to play significant functions in tumorigenesis and development. The association between PKM2 and NQO1 in breast cancer continues, however, to be unclear. In the present study, according to UALCAN and GEPIA database, the mRNA levels of PKM2 and NQO1 in breast primary tumor were significantly higher compared to normal breast tissue. Consonant with these findings, increased expression of both PKM2 and NQO1 were detected in clinical samples and BC cell lines. More importantly, consolidated high expression of NQO1 and PKM2 were obtained to be related with worse clinical stage, relapse, shorter relapse free survival (RFS), and poorer overall survival (OS) in human breast cancer. We subsequently found that knockdown of NQO1 reduced the protein level of PKM2 significantly. Moreover, deletion of PKM2 significantly reduced colony formation, migration and invasion of BC cells. A positive correlation between PKM2 and NQO1 expression was identified by immunohistochemical analyses of 108 specimens of breast cancer patients (rs = 0.60, P = 0.00). Finally, endogenous Co-IP demonstrated that PKM2 and NQO1 interact in breast cancer cells. The results of this study suggest that the correlation between NQO1 and PKM2 might play a critical role during breast tumourigenesis and serve as novel diagnostic biomarkers for breast cancer. 相似文献
8.
Dimitrios Stagos Gregorios D. Amoutzias Antonios Matakos Argyris Spyrou Aristides M. Tsatsakis Dimitrios Kouretas 《Food and chemical toxicology》2012
Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most frequent tumors representing the fifth commonest malignancy worldwide and the third cause of mortality from cancer. Currently, the treatments for HCC are not so effective and new strategies are needed for its fight. Chemoprevention, the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenesis is considered an important way for confronting HCC. Many of the chemopreventive agents are phytochemicals, namely non-nutritive plant chemicals with protective or disease preventive properties. In this review, we focus on plant polyphenols, one of the most important classes of phytochemicals, their chemopreventive properties against HCC and discuss the molecular mechanisms accounting for this activity. 相似文献
9.
Taiko Oda Weifang Wang Ayako Fujita Masataka Mochizuki Kazuyo Ukai Michio Namikoshi 《Journal of natural medicines》2007,61(4):434-437
An extract of a marine sponge, Hippospongia sp., collected in Palau has inhibitory activity against colony formation by Chinese hamster V79 cells. Bioassay-guided isolation
gave eleven sesquiterpene quinones. Compounds 1–8 inhibited colony formation by V79 cells with EC50 values between 0.6 and 2.8 μmol L−1. Their effects on the production of an inflammatory cytokine, IL-8, in tetradecanoyl phorbol acetate (PMA)-stimulated HL-60
cells were also investigated, because IL-8 production is sometimes correlated with inhibition of cell growth. Ilimaquinone
(1) and its 5 epimer (2) had similar activity against V79 cells (EC50 = 2.8 and 2.3 μmol L−1, respectively) but did not modulate IL-8 production even at 10 μmol L−1. Smenospongidine (3) and its 5 epimer (4), smenospongiarine (5) and its 5 epimer (6), and smenospongine (7) and its 5-epimer (8), at 10 μmol L−1, promoted IL-8 production. Compounds 3, 5, and 7 had slightly stronger activity against V79 cells (EC50 = 0.6, 1.7, and 0.8 μmol L−1, respectively) than the corresponding 5 epimers 4, 6, and 8 (EC50 = 0.8, 2.3, and 2.0 μmol L−1, respectively). A similar structure–activity relationship was observed for promotion of IL-8 production. This is the first
report of modulation of IL-8 production by these sesquiterpene quinones. 相似文献
10.
Everett SA Swann E Naylor MA Stratford MR Patel KB Tian N Newman RG Vojnovic B Moody CJ Wardman P 《Biochemical pharmacology》2002,63(9):1629-1639
3-(4-Methylcoumarin-7-yloxy)methylindole-4,7-diones were synthesised as model prodrugs in order to investigate the correlation between rates of reductive elimination from the (indolyl-3-yl)methyl position with reductive metabolism by hypoxic tumor cells and NADPH: cytochrome P450. Rates of elimination of the chromophore/fluorophore (7-hydroxy-4-methylcoumarin) following one-electron reduction of indolequinones to their semiquinone radicals (Q*-) was measured by pulse radiolysis utilising spectrophotometric and fluorometric detection. Incorporation of a thienyl or methyl substituent at the (indol-3-yl)CHR-position (where R=thienyl or methyl adjacent to the phenolic ether linking bond) significantly shortened the half-life of reductive elimination from 87 to 6 and 2 ms, respectively. Elimination from the methyl substituted analogue can thus compete effectively with the reaction of the semiquinone radical with oxygen at levels typically present in tumours (half-life approximately 1.8 ms at 0.5% O2). Chemical kinetic predictions were confirmed by metabolism in breast tumour MCF-7 cells between 0-2.1% O2. Rates of reductive release of the fluorophore from the non-fluorescent parent indolequinones (R=H, Me, thienyl) were similar under anoxia ( approximately 1.7 nmol coumarinmin(-1)mg protein(-1)) reflecting the similarity in one-electron reduction potential. Whereas coumarin release from the indolequinone (R=H) was completely inhibited above 0.5% O2, the enhanced rate of reductive elimination when R=thienyl or Me increased the metabolic rate of release to approximately 0.35 and 0.7 nmol coumarinmin(-1)mg protein(-1), respectively at 0.5% O2; complete inhibition occurring by 2.1% O2. Similar 'oxygen profiles' of release were observed with NADPH: cytochrome P450 reductase. In conclusion, it is possible to modify rates of reductive elimination from indolequinones to control the release of drugs over a range of tumour hypoxia. 相似文献