Cairo, Egypt

Misr International University is an undergraduate private university located in the suburbs of Cairo. Established in 1996, in Maadi, The University changed its location to km 28 Cairo-Ismailia Road. Wikipedia.

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Mowafy S.,Misr International University | Farag N.A.,Misr International University | Abouzid K.A.M.,Ain Shams University
European Journal of Medicinal Chemistry | Year: 2013

4-Anilino-6-substituted-quinazolines were designed, synthesized and evaluated for EGFR-TK and tumor growth inhibitory activities. The target compounds were designed with enamine ester or urea moieties appended at the C-6 of quinazoline as additional hydrogen bond acceptor functions. Most of the synthesized compounds displayed potent EGFR-TK inhibitory activity at 10 μM and the 6-ureido-anilinoquinazoline derivative 7a showed IC50 value of 0.061 μM. Moreover, six compounds were tested by National Cancer Institute (NCI), USA for their anti-proliferative activity at 10 μM in full NCI 60 cell panel. Compound 7a was further assayed for five dose molar ranges in full NCI 60 cell panel and exhibited remarkable growth inhibitory activity pattern against Non-Small Cell Lung Cancer EKVX (GI50 = 0.37 μM), NCI-H322M (GI50 = 0.36 μM), Renal Cancer A498 (GI50 = 0.46 μM), TK-10 (GI50 = 0.99 μM) and Breast Cancer MDA-MB-468 (GI50 = 1.096 μM) which are of high EGFR expression. Docking study was performed for the active compounds into ATP binding site of EGFR-TK which showed similar binding mode to gefitinib and additional binding with Cys-773 at the gatekeeper of EGFR-TK enzyme. © 2012 Elsevier Masson SAS. All rights reserved.

Elmazar M.M.,British Universityin Cairo | El-Abhar H.S.,Cairo University | Schaalan M.F.,Misr International University | Farag N.A.,Misr International University
PLoS ONE | Year: 2013

Since activation of PPARγ is the main target for the antidiabetic effect of TZDs, especially when it heterodimerizes with RXR, we aimed to test the potential antidiabetic effect of phytol (250 mg/kg), the natural precursor of phytanic acid, a RXR ligand and/or pioglitazone (5 mg/kg) to diabetic insulin-resistant rats. Regarding the molecular docking simulation on PPARγ, phytanic acid, rather than phytol, showed a binding mode that mimics the crystal orientation of rosiglitazone and pioglitazone, forming H bonds with the same amino acids (S289, H 323, H 449 and Y 473), and the least energy level, which emphasizes their importance for PPARγ molecular recognition, activation, hence antidiabetic activity. In addition, docking on the RXRα/PPARγ heterodimer, revealed that phytanic acid has higher binding affinity and lesser energy score on RXRα, compared to the original ligand, retinoic acid. Phytanic acid binds by 3H bonds and shares retinoic acid in arginine (R 316). These results were further supported biochemically, where oral phytol and/or pioglitazone (5 mg/kg) improved significantly glucose homeostasis, lipid panel, raised serum adiponectin level and lowered TNF-α, reaching in most cases the effect of the 10 mg/kg pioglitazone. The study concluded that the insulin sensitizing/anti-diabetic effect of phytol is mediated by partly from activation of nuclear receptors and heterodimerization of RXR with PPARγ by phytanic acid. © 2013 Elmazar et al.

Uhal B.D.,Michigan State University | Li X.,University of Iowa | Xue A.,Medical College of Wisconsin | Gao X.,Michigan State University | Abdul-Hafez A.,Misr International University
American Journal of Physiology - Lung Cellular and Molecular Physiology | Year: 2011

Earlier work from this laboratory demonstrated that apoptosis of alveolar epithelial cells (AECs) requires autocrine generation of angiotensin (ANG) II. More recent studies showed that angiotensin converting enzyme-2 (ACE-2), which degrades ANGII to form ANG1-7, is protective but severely downregulated in human and experimental lung fibrosis. Here it was theorized that ACE-2 and its product ANG1-7 might therefore regulate AEC apoptosis. To evaluate this hypothesis, the AEC cell line MLE-12 and primary cultures of rat AECs were exposed to the profibrotic apoptosis inducers ANGII or bleomycin (Bleo). Markers of apoptosis (caspase-9 or -3 activation and nuclear fragmentation), steady-state ANGII and ANG1-7, and JNK phosphorylation were measured thereafter. In the absence of Bleo, inhibition of ACE-2 by small interfering RNA or by a competitive inhibitor (DX600 peptide) caused a reciprocal increase in autocrine ANGII and corresponding decrease in ANG1-7 in cell culture media (both P < 0.05) and, moreover, induced AEC apoptosis. At baseline (without inhibitor), ANG1-7 in culture media was 10-fold higher than ANGII (P < 0.01). Addition of purified ANGII or bleomycin-induced caspase activation, nuclear fragmentation, and JNK phosphorylation in cultured AECs. However, preincubation with ANG1-7 (0.1 μM) prevented JNK phosphorylation and apoptosis. Moreover, pretreatment with A779, a specific blocker of the ANG1-7 receptor mas, prevented ANG1-7 blockade of JNK phosphorylation, caspase activation, and nuclear fragmentation. These data demonstrate that ACE-2 regulates AEC survival by balancing the proapoptotic ANGII and its antiapoptotic degradation product ANG1-7. They also suggest that ANG1-7 inhibits AEC apoptosis through the ANG1-7 receptor mas. © 2011 the American Physiological Society.

Alghool S.,Port Said University | Zoromba M.S.,Port Said University | El-Halim H.F.A.,Misr International University
Journal of Rare Earths | Year: 2013

Complexes of La (III), Nd(III), Gd(III), Sm(III), and Ce(IV) were synthesized with Schiff base [(3,5-di-tert-butyl-2-hydroxybenzyl) amino] acetic acid (H3L). The ligand and its complexes were synthesized and characterized based on the following analysis: elemental analyses, FAB-mass, molar conductance measurements, magnetic measurement, UV-visible, IR, and NMR spectral studies. The spectral data revealed that the ligand acted as a neutral tridentate coordinating to metal ion through ONO donor sequence. Thermal degradation studies of the ligand and its complexes showed that the previous lanthanide complexes were more thermally stable than the ligand itself. The Schiff base and its complexes were screened for their antibacterial (Escherichia coli, Staphylococcus aureus) and antifungal (Aspergillus flavus and Candida Albicans). © 2013 The Chinese Society of Rare Earths.

Schaalan M.F.,Misr International University | Nassar N.N.,Cairo University
Neurochemical Research | Year: 2011

Impairment of neuroendocrine, immune and antioxidant defenses contribute to pathophysiology of stress-induced depression. Somatostatin executes diverse regulatory effects on endocrine, exocrine and neural functions; however, the possibility that octreotide, a synthetic somatostatin analogue might mitigate stress-induced depression remains elusive. Hence, the current study aimed to explore the immunomodulatory and antioxidant effects of octreotide in a model of chronic mild stress (CMS). This paradigm was performed by exposing rats to a combination of mild unpredictable stressors for 21 days. Fifty male Wistar rats were divided into five groups; (1) control receiving saline, (2) octreotide given to normal unstressed animals. The remaining three groups were subjected to (3) CMS alone or in combination with octreotide (4) 50 μg/kg or (5) 90 μ/kg. Octreotide increased sucrose preference index and attenuated CMS-induced increases in plasma adrenocorticotrophic hormone and corticosterone levels. In addition, octreotide decreased plasma tumor necrosis factoralpha concentration. Moreover, it prevented CMS-induced oxidative damage by enhancing the antioxidant defenses superoxide dismutase, glutathione reductase and glutathione in the hippocampus. Furthermore, octreotide normalized the elevated malondialdehyde and lactate dehydrogenase levels in the hippocampus. These results demonstrate a possible antidepressant-like activity of octreotide in CMS due to its antioxidant/antiinflammatory aptitude. © Springer Science+Business Media, LLC 2011.

Schaalan M.F.,Misr International University | Mohamed W.A.,Cairo University | Amin H.H.,Al - Azhar University of Egypt
World Journal of Gastroenterology | Year: 2012

AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type III pro-collagen (PIIINP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 age- and sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC). Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH)2-Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PIIINP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PIIINP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PIIINP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PIIINP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PIIINP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PIIINP highlight their involvement in the immune response in patients with HCV-4- related liver diseases in Egypt. © 2012 Baishideng. All rights reserved.

Sherif S.,Misr International University | Bendas E.R.,Cairo University | Badawy S.,Misr International University
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2014

Topical 5% alpha lipoic acid (ALA) has shown efficacy in treatment of photo-damaged skin. The aim of this work was to evaluate the potential of poloxamer (P407) gel as a vehicle for the novel lipid base particulate system (cubosome dispersions) of ALA. Cubosome dispersions were formulated by two different approaches, emulsification of glyceryl monoolein (GMO) and poloxamer (P407) in water followed by ultrasonication, and the dilution method using a hydrotrope. Three different concentrations of GMO were used to formulate the cubosome dispersions using the first method, 5% (D1), 10% (D2) and 15% w/w (D3). In the second technique an isotropic liquid was produced by combining GMO with ethanol, and this isotropic liquid was then diluted with a P407 solution (D4). The dispersions were characterized by zeta potential, light scattering techniques, optical and transmission electron microscopy, encapsulation efficiency and in vitro drug release. Results showed that D4 was not a uniform dispersion and that D1, D2 and D3 were uniform dispersions, in which by increasing the GMO content in the dispersion, the size of the cubosomes decreased, zeta potential became more negative, encapsulation efficiency increased up to 86.48% and the drug release rate was slower. P407 gels were prepared using the cold method. Two concentrations of P407 gel were fabricated, 20 and 30% w/w. P407 gels were loaded with either ALA or dispersions containing ALA cubosomes. P407 gels were characterized by critical gelation temperature, rheological measurements and in vitro drug release studies. Results suggested that by increasing P407 concentration, the gelation temperature decreases and viscosity increases. Drug release in both cases was found to follow the Higuchi square root model. Gel loaded with ALA cubosomes provided a significantly lower release rate than the gel loaded with the un-encapsulated ALA. A double blinded placebo controlled clinical study was conducted, aiming to evaluate the efficacy as an anti-wrinkle agent and volunteer's satisfaction upon application of topical 30% P407 gel loaded with ALA cubosomes. Results indicated reduction in facial lines, almost complete resolution of fine lines in the periorbital region and upper lip area and overall improvement in skin color and texture in most volunteers. There were no instances of irritation, peeling or other apparent adverse side effects. © 2013 Elsevier B.V. All rights reserved.

El-Abhar H.S.,Cairo University | Schaalan M.F.,Misr International University
PLoS ONE | Year: 2012

Topiramate is an antiepileptic drug known to ameliorate insulin resistance besides reducing body weight. Albeit liver plays a fundamental role in regulation of overall insulin resistance, yet the effect of topiramate on this organ is controversial and is not fully investigated. The current work aimed to study the potential hepatic molecular mechanistic cassette of the anti-insulin resistance effect of topiramate. To this end, male Wistar rats were fed high fat/high fructose diet (HFFD) for 10 weeks to induce obese, insulin resistant, hyperglycemic animals, but with no overt diabetes. Two HFFD-groups received oral topiramate, 40 or 100 mg/kg, for two weeks. Topiramate, on the hepatic molecular level, has opposed the high fat/high fructose diet effect, where it significantly increased adiponectin receptors, GLUT2, and tyrosine kinase activity, while decreased insulin receptor isoforms. Besides, it improved the altered glucose homeostasis and lipid profile, lowered the ALT level, caused subtle, yet significant decrease in TNF-α, and boosted adiponectin in a dose dependent manner. Moreover, topiramate decreased liver weight/, visceral fat weight/, and epididymal fat weight/body weight ratios. The study proved that insulin-resistance has an effect on hepatic molecular level and that the topiramate-mediated insulin sensitivity is ensued partly by modulation of hepatic insulin receptor isoforms, activation of tyrosine kinase, induction of GLUT2 and elevation of adiponectin receptors, as well as their ligand, adiponectin, besides its known improving effect on glucose tolerance and lipid homeostasis. © 2012 El-Abhar, Schaalan.

Farag N.A.H.,Misr International University | El-Tayeb W.,Misr International University
European Journal of Medicinal Chemistry | Year: 2010

A number of new furobenzopyranones and pyranobenzopyranones carrying an electron- withdrawing function at the position 3 are synthesized in order to obtain new photoreagents towards DNA. Our interest in this study is to investigate the effect of introduction of electron withdrawing function on the position 3 of the benzo-á-pyranone ring of linear furobenzo-á-pyranone (5,8-dimethoxypsoralen) or angular pyranobenzo-á-pyranone on the biological activity, by preparing 3-cyano, carboxylic acid, carboxylic acid ester, acid hydrazide, thiosemicarbazide, or mercaptotriazole derivatives. 5-acetyl-6-hydroxybenzofuran, and 8-acetyl-7-hydroxy-4-phenylbenzopyranone are the key starting compounds on which 3-cyano-4-methylfurobenzopyranone and 3-cyano-4-methyl pyranobenzopyranone moieties were built respectively. The photobiological activity of the newly synthesized compounds was evaluated. It looks most promising for enhancement of photoreactivity of compounds towards DNA, and a certain effect was observed in the dark determining the antimicrobial activity. Compounds 5, 6, 7, 13, 14 exhibit potential photoreactivity towards DNA, while 3-mercaptotriazole derivatives 7, 14 possess only photosensitizing activity. To investigate the antimicrobial data on structural basis, molecular modelling and docking studies of the tested compounds into the crystal structure of topoisomerase II DNA Gyrase B complexed with the natural inhibitor bearing the coumarin moiety clorobiocin (1kzn), using Molsoft ICM 3.4-8C program was performed in order to predict the affinity and orientation of the synthesized compounds at the active site. The ICM score values and hydrogen bonds formed with the surrounding amino acids show good agreement with predicted binding affinities obtained by molecular docking studies as verified by antimicrobial screening, where compounds 5, 6, 13 were the most active compounds against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. Compound 13 has good affinity with the receptor and forms six hydrogen bonds with Asp-73, and two bonds with Thr-165, compound 6 has ICM score value -85.66 and forms one hydrogen bond with Asp-73, and three with Thr-165, and compound 5 has ICM score value -53 but forms one hydrogen bond with Asp-73, and four bonds with Thr-165 which may reveal the potent antimicrobial activity referred to the natural antimicrobial Clorobiocin which forms two hydrogen bonds with Asp-73 and three with Thr-165. © 2009 Elsevier Masson SAS. All rights reserved.

Abd El-Halim H.F.,Misr International University | Omar M.M.,Cairo University | Mohamed G.G.,Cairo University
Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy | Year: 2011

Schiff base (L) ligand is prepared via condensation of pyridine-2,6- dicarboxaldehyde with -2-aminopyridine. The ligand and its metal complexes are characterized based on elemental analysis, mass, IR, solid reflectance, magnetic moment, molar conductance, and thermal analyses (TG, DTG and DTA). The molar conductance reveals that all the metal chelates are non-electrolytes. IR spectra shows that L ligand behaves as neutral tridentate ligand and bind to the metal ions via the two azomethine N and pyridine N. From the magnetic and solid reflectance spectra, it is found that the geometrical structures of these complexes are octahedral (Cr(III), Fe(III), Co(II), Ni(II), Cu(II), and Th(IV)) and tetrahedral (Mn(II), Cd(II), Zn(II), and UO 2(II)). The thermal behaviour of these chelates shows that the hydrated complexes losses water molecules of hydration in the first step followed immediately by decomposition of the anions and ligand molecules in the subsequent steps. The activation thermodynamic parameters, such as, E*, ΔH*, ΔS* and ΔG* are calculated from the DTG curves using Coats-Redfern method. The synthesized ligand, in comparison to their metal complexes also was screened for its antibacterial activity against bacterial species, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus pyogones and Fungi (Candida). The activity data shows that the metal complexes to be more potent/antibacterial than the parent Schiff base ligand against one or more bacterial species. © 2010 Elsevier B.V. All rights reserved.

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