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21.
Mostafa M. Ghorab Fatma A. Ragab Helmy I. Heiba Hanan A. Youssef Marwa G. El-Gazzar 《Bioorganic & medicinal chemistry letters》2010,20(21):6316-6320
Pyrroles and pyrrolo[2,3-d]pyrimidines were reported to act as potent anticancer agents, in this work, a series of novel 2-substituted-3-cyano-4-phenyl-pyrrole 5, 6, 11–18, and 5-phenyl-pyrrolo[2,3-d]pyrimidine derivatives 7–10, 19–24 bearing either sulfathiazole or sulfapyridine were synthesized. The structures of these compounds were confirmed by elemental analysis, IR, 1H NMR and mass spectral data. All the newly synthesized compounds were evaluated for their in vitro cytotoxicity against liver and breast cancer cell line (HEPG2 and MCF7). Most of the screened compounds showed interesting cytotoxic activities compared with the used reference drug (doxorubicin). The radiosensitizing ability of some of the synthesized compounds was studied and the results showed an increase in the cell killing effect of γ-radiation after combination with the tested compounds. 相似文献
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Several potential cues for increased surface antigenic expression of lung-stage schistosomula, such as lack of glucose and amino acids and extremes of pH or HCO3- concentration, failed to alter the negligible larval reactivity with control, infection, or irradiated cercariae-vaccine serum in indirect membrane immunofluorescence. In contrast, incubation of larvae in 90% corn oil for 6 hr led to surface membrane changes, which allowed specific and strong binding of antibody from antischistosome sera. The data together indicated that the lung-stage worms' confinement of antigenic molecules in lipid-rich sites of the outer membrane could be reversed in vitro after exposure to corn oil, in a concentration- and time-dependent manner. 相似文献
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Mostafa M. Ghorab Fatma A. Ragab Helmy I. Heiba Marwa G. El-Gazzar Mostafa G.M. El-Gazzar 《Bioorganic & medicinal chemistry letters》2018,28(9):1464-1470
In this study, novel series of thioureido-benzenesulfonamide derivatives bearing an enaminone linker either meta or para oriented and having terminal linear or substituted aromatic or heteroaromatic ring system 5–16a,b were designed and synthesized based on the general pharmacophoric features of type II VEGFR2 inhibitors. Evaluation of the synthesized compounds against HEPG2 hepatocellular carcinoma cells in vitro identified compounds 5b, 6b and 10–13b as most active anticancer agents with IC50 equal to 0.12, 0.29, 0.58, 0.44, 0.42 and 0.66?µM, respectively. These compounds were evaluated for their ability to in vitro inhibit VEGFR2 kinase enzyme. The results demonstrated highly potent dose-related VEGFR2 inhibition with IC50 values in nanomolar range (33, 57, 210, 37, 37 and 220?nM, respectively). The radiosensitizing ability of the most promising compounds was studied which showed an increase in the cell killing effect of radiation after combination with the synthesized compounds which revealed lowered IC50 by nearly 50%. Molecular docking for the most potent compounds was performed to predict their possible binding mode within VEGFR2 active site and they showed binding affinity in a similar way to sorafenib. 相似文献
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Shadia E. Ramadan A. A. Razak Y. A. Yousseff N. M. Sedky 《Biological trace element research》1988,18(1):161-170
Fusarium sp. was isolated from Sinai soil at Egypt. It showed tendency to tolerate high concentrations of selenium in the form of sodium
selenite up to 3.5% (w/v). The microscopic examination revealed some morphological distortions. However, the fungus was capable
to circumvent the toxic effect of selenium. The fungus possesses strong reducing ability as high quantities of elemental selenium
were precipitated within the fungal cells as well as on the surface of the fungal hyphae and spores. The presence of selenium
increased the cellular contents of carbohydrates, proteins, and lipids. Labeling studies indicate the incorporation of selenite
into certain amino acids: selenocysteine and selenocysteic acid. Moreover, the presence of selenium induced the biosynthesis
of several types of low molecular weight proteins. The results demonstrated different modes of detoxification of selenium
toxicity. 相似文献
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Thrombin-induced extracellular signal-regulated kinase 2 (ERK2) activation is negatively regulated in conditions of all bP3 integrin engagement and platelet aggregation. Here we show by Western blotting with antibodies against mono- and biphosphorylated forms of ERK2 that the dephosphorylation of ERK2 by alpha llb beta 3 engagement affects threonine183 and not tyrosine185. Addition of a potent serine/threonine phosphatase inhibitor, okadaic acid (OA), restored thrombin-induced threonine phosphorylation of ERK2 in conditions of platelet aggregation, whereas OA had no effect in the absence of alpha llb beta 3 engagement. These observations are consistent with alpha llb beta 3 engagement acting via at least one serine/threonine phosphatase,which dephosphorylates the phosphothreonine183 residue of ERK2. Moreover, a small amount (14%) of ERK2 was translocated to the alpha llb beta 3-dependent cytoskeleton, mostly ina monophosphorylated (i.e. inactive) form, suggesting that cytoskeleton-associated ERK2 plays only a minor role, if any. Finally, we show that negative regulation (i.e. dephosphorylation)occurs primarily or totally in the cytosol and that the alpha llb beta 3-dependent ERK2 Thr183-specific phosphatase is different from phosphatase 1 (PP1) or PP2A. We conclude that all alpha llb beta 3 engagement down-regulates ERK2 through selective dephosphorylation of the phosphothreonine183 residue by a cytosolic serine/threonine phosphatase different from known platelet phosphatases. 相似文献
27.
Wissam H. Faour Mohamed Mroueh Costatantine F. Daher Hanan M. Ragab Asser I. Ghoneim 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):1079-1094
Four series of new bipyrazoles comprising the N-phenylpyrazole scaffold linked to polysubstituted pyrazoles or to antipyrine moiety through different amide linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory and analgesic activities. In vitro COX-1/COX-2 inhibition study revealed that compound 16b possessed the lowest IC50 value against both COX-1 and COX-2. Moreover, the effect of the most promising compounds on inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) protein expression in lipopolysaccharide (LPS)-activated rat monocytes was also investigated. The results revealed that some of the synthesized compounds showed anti-inflammatory and/or analgesic activity with less ulcerogenic potential than the reference drug diclofenac sodium and are well tolerated by experimental animals. Moreover, they significantly inhibited iNOS and COX-2 protein expression induced by LPS stimulation. Compounds 16b and 18 were proved to display anti-inflammatory activity superior to diclofenac sodium and analgesic activity equivalent to it with minimal ulcerogenic potential. 相似文献
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Preparation of rat liver lysosomes 总被引:10,自引:0,他引:10