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铀化合物在国防工业和国民经济建设中有十分重要的地位,但其通过各种途径(主要是吸入)进入人体后对人体造成的危害却十分严重。陈文致、徐美忠等曾对几种新的膦酸类和含邻苯二酚残基的化合物进行研究,发现它们对铀的促排效果比钛铁试剂更好。为进一步探讨含邻苯二酚残基的螯合剂对铀促排的构效关系,我们合成了12种2,3-二羟基-4-甲氧羰基苄基胺羧酰胺类化合物(Ⅳ),并进行了多种金属的解毒试验。以生产香料香兰素的副产物邻香兰素(o-vanillin)为起始原料,经八步反应得到目标化合物(Scheme 1)。 相似文献
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Kam-Meng Tchou-Wong Sandra YY Fok Jeffrey S Rubin Fiona Pixley John Condeelis Filip Braet William Rom Lilian L Soon 《BMC cancer》2007,7(1):32
This is a correction of an earlier published article. 相似文献
105.
Hannah YY Lee PhD James D Morton PhD Lucinda JG Robertson PhD Joshua D McDermott MSc Roy Bickerstaffe PhD Andrew D Abell PhD Matthew A Jones PhD Janna M Mehrtens PhD James M Coxon PhD 《Clinical & experimental ophthalmology》2008,36(9):852-860
Purpose: The aim of this study is to evaluate the therapeutic potential of a newly synthesized calpain inhibitor, CAT0059, using a naturally occurring in vivo sheep cataract model. Methods: The selectivity of CAT0059 was investigated by an in vitro protease assay. The efficacy of CAT0059 in preventing proteolysis of lens cytoskeletal proteins by calpain 2 was investigated using a lens‐based cell‐free method. The cytotoxicity and stability of CAT0059 in physiological conditions were examined using cultured sheep lenses. Protein binding of CAT0059 by ocular proteins was assessed and quantified by a modified high‐performance liquid chromatography assay. CAT0059 was formulated in an eye drop solution and as an eye ointment. These were applied in vivo daily to one eye of the cataract lambs, over a 67‐ and 97‐day trial period, respectively. The progression of cataracts in the treated and untreated eyes was assessed by an independent veterinary ophthalmologist using a slit‐lamp microscope. Results: In vitro assays revealed that CAT0059 was selective for cysteine proteases and also protected lens cytoskeletal proteins from degradation. CAT0059 was stable in physiological conditions and non‐toxic to the lens. Only 15% of CAT0059 is bound to proteins in the aqueous humour but >90% bound to lens homogenate. The 67‐day CAT0059 eye drop treatment was not effective in slowing the rate of cataract development. However, application of CAT0059 in an eye ointment initially slowed cataract development compared with the untreated eye. This effect was temporary. Conclusions: In vitro assays confirmed CAT0059 to be a potent calpain inhibitor. The two in vivo trials addressed the ability of CAT0059 to reach the lens and established its limitations as a therapeutic molecule for cataract treatment. 相似文献
106.
Antifungal activity of natural products is being studied widely. Saponins are known to be antifungal and antibacterial. We used bioassay-guided fractionation to have isolated eight steroid saponins from Tribulus terrestris L. , which were identified as hecogenin-3-O-beta-D-glucopyranosyl ( 1→4 )-beta-D-galactopyranoside ( TTS-8), tigogenin-3-O-beta-D-glucopyranosyl ( 1 →4 )-beta-D-galactopyranoside ( TTS-9 ), hecogenin-3-O-beta-D-glucopyranosyl ( 1 → 2 )-beta-D-glucopyranosyl ( 1 4 )-beta-D-galactopyranoside ( TTS-10 ), hecogenin-3-O-beta-D-xylopyranosyl ( 1→3 )-beta-D-glucopyranosyl ( 1→ 4 )-beta-D-galactopyranoside ( TTS-11 ), tigogenin-3-O-beta-D-xylopyranosyl ( 1→ 2 )-[- beta-D-xylopyranosyl ( 1 → 3 ) ]-beta-D-glucopyranosyl (1→4)-[alpha-L-rhamnopyranosyl (1→2)]-beta-D-galactopyranoside (TTS-12), 3-O-Ebeta-D-xylopyranosyl (1→2)-[beta-D- xylopyranosyl (1→3)]-beta-D-glucopyranosyl ( 1→4)-[alpha-L-rhamnopyranosyl ( 1→2 )]-beta-D-galactopyranosy13-26-O-beta- D-glucopyranosyl-22-methoxy-(3beta, 5alpha, 25R)-furostan-3,26-diol (TTS-13), hecogenin-3-O-beta-D-glucopyranosyl ( 1→ 2)-[beta-D-xylopyranosyl ( 1→ 3 )]-beta-D-glucopyranosyl ( 1 → 4 )-beta-D-galactopyranoside ( TTS-14 ), tigogenin-3-O-beta-D- glucopyranosyl ( 1→ 2 )-[ beta-D-xylopyranosyl ( 1 → 3 )]-beta-D-glucopyranosyl ( 1 → 4 )-beta-D-galaetopyranoside ( TTS-15 ). The in vitro antifungal activities of the eight saponins against five yeasts, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Cryptococcus neoformans were studied using microbroth dilution assay. In vivo activity of TTS-12 in a Candida albicans vaginal infection model was studied in particular. The results showed that TTS-12 and TTS-15 were very effective against several pathogenic candidal species and Cryptococcus neoformans in vitro. It is noteworthy that TTS-12 and TTS-15 were very active against Candida albicans (MIC50 = 10 and 2.3 microg/ml) and Cryptococcus neoformans (MIC50 = 1.7 and 6. 7 microg/ml). 相似文献
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Modriansky M Tyurina YY Tyurin VA Matsura T Shvedova AA Yalowich JC Kagan VE 《Toxicology》2002,177(1):105-117
Effective scavenging of reactive radicals and low reactivity of generated secondary antioxidant radicals towards vital intracellular components are two critical requirements for a chain-breaking antioxidant. Tubulin-binding properties aside, colchicine metabolites remain largely untested for other possible biological activities, including antioxidant activity. Mourelle et al. [Life Sci. 45 (1989) 891] proposed that colchiceine (EIN) acts as an antioxidant and protective agent against lipid peroxidation in a rat model of liver injury. Since EIN as well as two other colchicine metabolites, 2-demethylcolchicine (2DM) and 3-demethylcolchicine (3DM), possess a hydroxy-group on their carbon ring that could participate in radical scavenging, we tested whether they can act as chain-breaking antioxidants. Using our fluorescence-HPLC assay with metabolically incorporated oxidation-sensitive cis-parinaric acid (PnA) we studied the effects of colchicine metabolites on peroxidation of different classes of membrane phospholipids in HL-60 cells. None of the colchicine metabolites in concentrations ranging from 10(-6) to 10(-4) M was able to protect phospholipids against peroxidation induced by either azo-initiators of peroxyl radicals or via myeloperoxidase (MPO)-catalyzed reactions in the presence of hydrogen peroxide. However, the metabolites did exhibit dose-dependent depletion of glutathione, resembling the behavior of etoposide, a hindered phenol with antioxidant properties against lipid peroxidation. Electron spin resonance (ESR) experiments demonstrated that in a catalytic system containing horseradish peroxidase (HRP)/H(2)O(2), colchicine metabolites undergo one-electron oxidation to form phenoxyl radicals that, in turn, cause ESR-detectable ascorbate radicals by oxidation of ascorbate. Phenoxyl radicals of colchicine metabolites formed through MPO-catalyzed H(2)O(2)-dependent reactions in HL-60 cells and via HRP/H(2)O(2) in model systems can also oxidize GSH. Thus, colchicine metabolites possess the prerequisites of many antioxidants, i.e. a nucleophilic hydroxy-group on a carbon ring and the ability to scavenge reactive radicals and form a secondary radical. However, the latter retain high reactivity towards critical biomolecules in cells such as lipids, thiols, ascorbate, thereby, rendering colchicine metabolites effective radical scavengers but not effective chain-breaking antioxidants. 相似文献
110.
瘤体内注射卡铂和消痔灵对荷瘤鼠的抗肿瘤作用及其毒性 总被引:3,自引:0,他引:3
目的:观察瘤内注射(it)卡铂(CBP)和消痔灵(XZL)的抗肿瘤作用。方法:选用小鼠S180实验体瘤模型,it XZL,it及静脉注射(iv)CBP治疗,测定各组小鼠的瘤重,体重,脾指数和胸腺指数。结果:与生理盐水(NS)组比较,iv CBP 30mg/kg,it XZL 10ml/kg和it CBP 30,60mg/kg的抑瘤率分别为20.23%和,25.6%,27.4%和41.9%,脾指数变化分别为-41.0%,12.2%-28.4和-49.2%,胸腺指数变化分别为-8.5%,33.0%,-5.3%和-12.8%。结论:it CBP和XZL均有抗肿瘤作用,CBP降低荷瘤鼠免疫器官指数,而ZL则增加荷瘤鼠免疫器官指数。 相似文献