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排序方式: 共有254条查询结果,搜索用时 15 毫秒
81.
82.
Khan KM Rahim F Halim SA Taha M Khan M Perveen S Zaheer-Ul-Haq Mesaik MA Iqbal Choudhary M 《Bioorganic & medicinal chemistry》2011,19(14):4286-4294
Benzothiazole derivatives 1-26 have been synthesized and their in vitro β-glucuronidase potential has been evaluated. Compounds 4 (IC(50)=8.9 ± 0.25 μM), 5 (IC(50)=36.1 ± 1.80 μM), 8 (IC(50)=8.9 ± 0.38 μM), 13 (IC(50)=19.4 ± 1.00 μM), 16 (IC(50)=4.23 ± 0.054 μM), and 18 (IC(50)=2.26 ± 0.06 μM) showed β-glucuronidase activity potent than the standard (d-saccharic acid 1,4-lactone, IC(50)=48.4 ± 1.25 μM). Compound 9 (IC(50)=94.0 ± 4.16 μM) is found to be the least active among the series. All active analogs were also evaluated for cytotoxicity and none of the compounds showed any cytotoxic effect. Furthermore, molecular docking studies were performed using the gold 3.0 program to investigate the binding mode of benzothiazole derivatives. This study identifies a novel class of β-glucuronidase inhibitors. 相似文献
83.
Castonguay R Halim D Morin M Furtos A Lherbet C Bonneil E Thibault P Keillor JW 《Biochemistry》2007,46(43):12253-12262
Gamma-glutamyltranspeptidase (GGT) is a heterodimeric enzyme important for glutathione homeostasis control. It has also been implicated in many physiological disorders, including Parkinson's disease, apoptosis inhibition, and diabetes. In the first step of its ping-pong mechanism it binds glutathione, its in vivo substrate, and releases cysteinylglycine upon formation of an acyl-enzyme intermediate. This intermediate can then react with water to release glutamate as a hydrolysis product or with an amino acid or dipeptide to form a transpeptidation product. Further detailed study of the mechanism underlying these reactions is hindered at least for some GGTs by the low quantities of protein available after a multistep purification from tissue. In the present work the gene for human GGT was cloned into the pPICZalphaA vector and transformed into Pichia pastoris to express as a 68 kDa His-tagged protein. The optimized expression and secretion of this enzyme in 1 L of culture and subsequent purification by immobilized metal affinity chromatography yielded 1.6 mg of purified enzyme having a specific activity of 237 U/mg. Kinetic parameters for the transpeptidation reaction between glutathione and glycylglycine were determined by mass spectrometry, giving a kcat of 13.4 x 10(3) min-1 and apparent KM values of 1.11 mM for glutathione and 8.1 mM for glycylglycine. The GGT-mediated hydrolysis of glutathione was also studied, providing a kcat of 53 min-1 and a KM value of 7.3 microM for glutathione. Incubation of the enzyme with a mechanism-based inhibitor, enzymatic digest, and mass spectrometric analysis provided the first unambiguous identification of Thr381 as the active site nucleophile of human gamma-glutamyltranspeptidase, and confirmed four of the seven N-linked glycosylation sites. These structural and kinetic data are discussed with respect to a homology model generated to facilitate visualization. 相似文献
84.
Xiaorong Fu Alexander Halim Boren Tian Qing Luo Guanbin Song 《Journal of cellular physiology》2019,234(8):14133-14144
Mobilization from the bone marrow and the migration of bone-marrow-derived mesenchymal stem cells (BMSCs) through the peripheral circulation to injured tissue sites are regulated by multiple mechanical and chemical factors. We previously demonstrated that mechanical stretching promotes the migration but inhibits the invasion of BMSCs. However, the involved mechanisms, especially the mechanism of stretching-inhibited BMSC invasion, have not been thoroughly elucidated to date. In this study, we found that mechanical stretching with a 10% amplitude at a 1-Hz frequency for 8 hr significantly reduces BMSC invasion and downregulates the expression of membrane type-1 matrix metalloproteinases (MT1-MMP) at both the messenger RNA and protein levels. The overexpression of MT1-MMP restores mechanical stretching-reduced BMSC invasion. Moreover, phosphatidylinositol 3-kinase (PI3K)-dependent Akt phosphorylation in BMSCs was found to be inactivated by mechanical stretching. Pharmacological inhibitors of PI3K/Akt signaling (LY294002 or A443654) reduced the expression of MT1-MMP and impaired BMSC invasion. In addition, the upregulation of Akt phosphorylation by a pharmacological activator (SC79) increased MT1-MMP expression and suppressed mechanical stretching-reduced BMSC invasion. Taken together, our results suggest that mechanical stretching inhibits BMSC invasion by downregulating MT1-MMP expression by suppressing the PI3K/Akt signaling pathway. 相似文献
85.
A novel sensitive and simple spectrofluorimetric method was developed then validated for determination of midodrine in both its authentic pure form and its tablets. This method is based on the reaction between midodrine's aliphatic primary amine moiety with fluorescamine reagent, using borate buffer at pH 7.8 and yielding a highly fluorescent product whose fluorescence intensity was measured at 462 nm after excitation at 388 nm. This method represents the first attempt for determination of midodrine spectrofluorimetrically. A calibration curve was constructed showing that the linear range was 0.2–3.0 μg/ml. The limit of detection and limit of quantitation values were 0.06 and 0.19 μg/ml respectively. The correlation coefficient (r) and the determination coefficient (r2) values were 0.9992 and 0.9984 respectively. The proposed method was validated according to ICH guidelines and successfully applied for determination of midodrine in its tablets with an overall % recovery of 99.56 ± 0.95. Finally, the presented method was adapted to study the content uniformity test according to United States Pharmacopeia guidelines. 相似文献
86.
87.
Abdel Halim Harrath Abdelhabib Semlali Lamjed Mansour Mukhtar Ahmed Alexander V. Sirotkin Suliman Y. Al Omar Maha Arfah Mohamed S. Al Anazi Ibrahim M. Alhazza Jens R. Nyengaard Saleh Alwasel 《Cell and tissue research》2014,358(2):607-620
Ex-fissiparous planarians produce infertile cocoons or, in very rare cases, cocoons with very low fertility. Here, we describe the features of programmed cell death (PCD) occurring in the hyperplasic ovary of the ex-fissiparous freshwater planarian Dugesia arabica that may explain this infertility. Based on TEM results, we demonstrate a novel extensive co-clustering of cytoplasmic organelles, such as lysosomes and microtubules, and their fusion with autophagosomes during the early stage of oocyte cell death occurring through an autophagic pattern. During a later stage of cell death, the generation of apoptotic vesicles in the cytoplasm can be observed. The immunohistochemical labeling supports the ultrastructural results because it has been shown that the proapoptotic protein bax was more highly expressed in the hyperplasic ovary than in the normal one, whereas the anti-apoptotic protein bcl2 was slightly more highly expressed in the normal ovary compared to the hyperplasic one. TUNEL analysis of the hyperplasic ovary confirmed that the nuclei of the majority of differentiating oocytes were TUNEL-positive, whereas the nuclei of oogonia and young oocytes were TUNEL-negative; in the normal ovary, oocytes are TUNEL-negative. Considering all of these data, we suggest that the cell death mechanism of differentiating oocytes in the hyperplasic ovary of freshwater planarians is one of the most important factors that cause ex-fissiparous planarian infertility. We propose that autophagy precedes apoptosis during oogenesis, whereas apoptotic features can be observed later. 相似文献
88.
Naif Mohammed Al-Hada Elias B. Saion Abdul Halim Shaari Mazliana A. Kamarudin Moayad Husein Flaifel Sahrim Hj Ahmad Salahudeen A. Gene 《PloS one》2014,9(8)
A facile thermal-treatment route was successfully used to synthesize ZnO nanosheets. Morphological, structural, and optical properties of obtained nanoparticles at different calcination temperatures were studied using various techniques. The FTIR, XRD, EDX, SEM and TEM images confirmed the formation of ZnO nanosheets through calcination in the temperature between 500 to 650°C. The SEM images showed a morphological structure of ZnO nanosheets, which inclined to crumble at higher calcination temperatures. The XRD and FTIR spectra revealed that the samples were amorphous at 30°C but transformed into a crystalline structure during calcination process. The average particle size and degree of crystallinity increased with increasing calcination temperature. The estimated average particle sizes from TEM images were about 23 and 38 nm for the lowest and highest calcination temperature i.e. 500 and 650°C, respectively. The optical properties were determined by UV–Vis reflection spectrophotometer and showed a decrease in the band gap with increasing calcination temperature. 相似文献
89.
90.