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301.
Zou R Kawashima E Freeman GA Koszalka GW Drach JC Townsend LB 《Nucleosides, nucleotides & nucleic acids》2000,19(1-2):125-153
Stereoselective glycosylation of 2,5,6-trichlorobenzimidazole (1b), 2-bromo-5,6-dichlorobenzimidazole (1c), 5,6-dichlorobenzimidazole (1d), 5,6-dichlorobenzimidazole-2-thione (1e), 5,6-dichloro-2-(methylthio)benzimidazole (1f), 2-(benzylthio)-5,6-dichlorobenzimidazole (1g), and 2-chloro-5,6-dimethylbenzimidazole (1h) with 2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofuranosyl chloride was achieved to give the desired beta nucleosides 2b-h. Subsequent deprotection afforded the corresponding free beta-D-2-deoxyribosides 3b-h. The 2-methoxy derivative 3i was synthesized by the treatment of 2b with methanolic sodium methoxide. Displacement of the 2-chloro group of 2b with lithium azide followed by a removal of the protective groups gave the 2-azido-5,6-dichlorobenzimidazole derivative (5). The 2-amino derivative (6) was obtained by hydrogenolysis of 5 over Raney nickel. 5,6-Dichloro-2-isopropylamino-1-(2-deoxy-beta-D-erythro- pentofuranosyl)benzimidazole (10) was prepared using 2'-deoxyuridine (7), N-deoxyribofuranosyl transferase and 1d followed by functionalization of the C2 position. Antiviral evaluation of target compounds established that compounds 3b and 3c were active against human cytomegalovirus (HCMV) at non-cytotoxic concentrations. The activity of these 2-deoxy ribosides, however, was less than the activity of the parent riboside, 2,5,6-trichloro-1-beta-D-ribofuranosylbenzimidazole (TCRB). Compared to TCRB, 3b and 3c were somewhat more cytotoxic and active against herpes simplex virus type 1. Compounds 3d-i with other substituents in the 2-position were inactive against both viruses and non-cytotoxic. In contrast, compounds with amine substituents in the 2-position (5, 6, 10) were active against HCMV albeit less so than TCRB. These results establish that 2-deoxy-D-ribosyl benzimidazoles are less active against the DNA virus HCMV than are the corresponding D-ribosides. 相似文献
302.
Zou CG Agar NS Jones GL 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2000,127(3):347-353
Haemolysis of red blood cells (RBC) in glycerol media may be measured spectrophotometrically. The haemolytic process in a rapid phase obeys a first order rate law. The rate constant expresses the rate of haemolysis. To gain a better understanding of the mechanism of haemolysis in glycerol media, the effects of pH and band 3 inhibitors on the rate of haemolysis in human and sheep RBC were observed. Over the pH range used (pH 5.8-10.0), the rate of haemolysis decreased with increase in pH in sheep RBC. By contrast, the rate of haemolysis increased from pH 5.8 to 6.4 and decreased above pH 6.4 in human RBC. The different effects of pH on the rate of haemolysis are due to inhibition of glycerol permeability by H(+) in human RBC but not in sheep RBC. This is supported by the different effects of temperature and Cu(2+) on the rate of haemolysis in human and sheep RBC. We did not observe complete inhibition of haemolysis by the classical band 3 inhibitor, 4, 4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Another band 3 inhibitor 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS) showed only weak inhibition. Phenylgloxal (PG), another band 3 inhibitor, had no effect whatsoever on the rate of haemolysis. These results indicate that the anion pathway of band 3 is not the preferred route of transport of glycerol in mammalian RBC. 相似文献
303.
Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress 总被引:37,自引:0,他引:37
Yan SF Fujita T Lu J Okada K Shan Zou Y Mackman N Pinsky DJ Stern DM 《Nature medicine》2000,6(12):1355-1361
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The clinical significance of thymidine kinase 1 measurement in serum of breast cancer patients using anti-TK1 antibody 总被引:5,自引:0,他引:5
He Q Zou L Zhang PA Lui JX Skog S Fornander T 《The International journal of biological markers》2000,15(2):139-146
The activity of total thymidine kinase in serum (S-TK) has been used as a tumor maker for decades. To date such activity has been determined using [125]I-iodo-deoxyuridine as a substrate. The aim of this study was to develop a new, antibody-based technique for the measurement of cytoplasmic thymidine kinase (TK1) in serum. Both mono- and polyclonal antibodies against S-TK1 were used in dot blot assay. S-TK1 was characterized by SDS and IEF techniques. Sixty-five breast cancer patients were studied, including 17 preoperative and 38 postoperative tumor-free patients and 10 patients with metastases to the lymph nodes (N1-2). They were compared to patients with benign tumors (n=21) and healthy volunteers (n=11). S-TK1 was low (0-1.0 pM) in healthy volunteers, while in preoperative patients the level was increased 6-110-fold. Significant differences were observed between preoperative patients and healthy volunteers (p=0.005), preoperative patients and patients with benign tumors (p<0.001), and preoperative patients and postoperative patients without metastases (p<0.001). No significant difference was observed between preoperative patients and postoperative patients with metastases (p=0.191). The S-TK activity in preoperative patients was also high in serum, but no decrease was observed following surgery. In conclusion, the anti-TK1 antibody could be a good marker for monitoring the response of breast cancer patients to therapy. 相似文献
307.
Effect of resveratrol on intimal hyperplasia after endothelial denudation in an experimental rabbit model 总被引:9,自引:0,他引:9
The ability of resveratrol to inhibit vascular intimal thickening was tested in an experimental model in which endothelial denudation was performed in the normal rabbit iliac artery. Resveratrol (2 approximately 4mg/ kg/d) was administered intragastrically for 5 weeks beginning 1 week before denudation. At the higher concentration of resveratrol, the intimal hyperplasia of injured vascular wall was effectively inhibited; the intimal proliferation index also was significantly less than that in the untreated control group (0.28 +/- 0.07 vs 0.41 +/- 0.13, respectively, p<0.01); the relative luminal area increased from 0.38 +/- 0.06 in the untreated control group to 0.53 +/- 0.10 in the resveratrol treatment group (p < 0.001); and the count of smooth muscle cells in the thickened intima was statistically significantly reduced in the high dose resveratrol treatment group than that in the untreated group (1,115 +/- 510 vs 1,796 +/- 963, respectively, p < 0.05). Resveratrol added to the culture media of cultured rabbit vascular smooth muscle cells inhibited DNA synthesis in a dose-dependent manner. These results showing that resveratrol is capable of inhibiting intimal hyperplasia of injured artery raise the possibility that this polyphenol might have clinical potential in prevention and treatment of restenosis after angioplasty. 相似文献
308.
309.
金线蛙入蛰时几项生理常数间的关系研究 总被引:1,自引:0,他引:1
本文经统计学分析处理,表明金钱蛙(Ranaplancyi)入蛰时的体长与体重、胴体重和体重与肝重、脂肪体重、生殖腺重之间均存在非常显著的线性相关关系。 相似文献
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