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4 results on '"Abdel-Nasser A. Sabra"'

1. Deciphering the enzymatic target of a new family of antischistosomal agents bearing a quinazoline scaffold using complementary computational tools

Author

Victor Sebastian-Perez, Alfonso García-Rubia, Sayed H. Seif el-Din, Abdel-Nasser A. Sabra, Naglaa M. El-Lakkany, Samia William, Tom L. Blundell, Louis Maes, Ana Martinez, Nuria E. Campillo, Sanaa S. Botros, and Carmen Gil

Subjects
drug discovery, quinazoline, schistosoma mansoni, target deconvolution, Therapeutics. Pharmacology, RM1-950
Abstract

A previous phenotypic screening campaign led to the identification of a quinazoline derivative with promising in vitro activity against Schistosoma mansoni. Follow-up studies of the antischistosomal potential of this candidate are presented here. The in vivo studies in a S. mansoni mouse model show a significant reduction of total worms and a complete disappearance of immature eggs when administered concomitantly with praziquantel in comparison with the administration of praziquantel alone. This fact is of utmost importance because eggs are responsible for the pathology and transmission of the disease. Subsequently, the chemical optimisation of the structure in order to improve the metabolic stability of the parent compound was carried out leading to derivatives with improved drug-like properties. Additionally, the putative target of this new class of antischistosomal compounds was envisaged by using computational tools and the binding mode to the target enzyme, aldose reductase, was proposed.

Published
2020
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2. Screening of a PDE-focused library identifies imidazoles with in vitro and in vivo antischistosomal activity

Author

Sanaa S. Botros, Samia William, Abdel-Nasser A. Sabra, Naglaa M. El-Lakkany, Sayed H. Seif el-Din, Alfonso García-Rubia, Victor Sebastián-Pérez, Antoni R. Blaazer, Erik de Heuvel, Maarten Sijm, Yang Zheng, Irene G. Salado, Jane C. Munday, Louis Maes, Iwan J.P. de Esch, Geert J. Sterk, Koen Augustyns, Rob Leurs, Carmen Gil, and Harry P. De Koning

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

We report the evaluation of 265 compounds from a PDE-focused library for their antischistosomal activity, assessed in vitro using Schistosoma mansoni. Of the tested compounds, 171 (64%) displayed selective in vitro activity, with 16 causing worm hypermotility/spastic contractions and 41 inducing various degrees of worm killing at 100 μM, with the surviving worms displaying sluggish movement, worm unpairing and complete absence of eggs. The compounds that did not affect worm viability (n = 72) induced a complete cessation of ovipositing. 82% of the compounds had an impact on male worms whereas female worms were barely affected. In vivo evaluation in S. mansoni-infected mice with the in vitro ‘hit’ NPD-0274 at 20 mg/kg/day orally for 5 days resulted in worm burden reductions of 29% and intestinal tissue egg load reduction of 35% at 10 days post-treatment. Combination of praziquantel (PZQ) at 10 mg/kg/day for 5 days with NPD-0274 or NPD-0298 resulted in significantly higher worm killing than PZQ alone, as well as a reduction in intestinal tissue egg load, disappearance of immature eggs and an increase in the number of dead eggs. Keywords: Phosphodiesterase, In vitro drug screening, Worm killing, Schistosoma mansoni, Mouse model, Praziquantel, Schistosomiasis

Published
2019
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3. Co-administration of metformin and N-acetylcysteine with dietary control improves the biochemical and histological manifestations in rats with non-alcoholic fatty liver

Author

Abdel-Nasser A. Sabra, Sayed H. Seif el-Din, Fatma A. Ebeid, Naglaa M. El-Lakkany, and Olfat Hammam

Subjects
medicine.medical_specialty, Very low-density lipoprotein, Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Pharmacy and materia medica, Internal medicine, NAFLD, medicine, Adipocytokines, General Pharmacology, Toxicology and Pharmaceutics, nafld, metformin, n-acetylcysteine, oxidative stress, adipocytokines, tnf-α, Adiponectin, Cholesterol, Fatty liver, nutritional and metabolic diseases, Malondialdehyde, medicine.disease, Metformin, N-acetylcysteine, RS1-441, Endocrinology, chemistry, Alanine transaminase, Oxidative stress, 030220 oncology & carcinogenesis, TNF-α, biology.protein, Original Article, Steatosis, 030217 neurology & neurosurgery
Abstract

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning health problem that affects 1/3 of the adult population and an increasing number of children in developed countries. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. This study was conceived in a NAFLD rat model to evaluate the efficacy of both metformin (MTF) and N-acetylcysteine (NAC) with dietary control on biochemical and histologic liver manifestations. Rats were classified into nine groups; normal (I), NAFLD-induced by feeding high-fat diet (HFD; II) for 12 weeks, NAFLD switched to regular diet (RD; III), NAFLD-HFD or -RD treated with MTF in a dose of 150 mg/kg (IV, V), NAC in a dose of 500 mg/kg (VI, VII) or MTF+NAC (VIII, IX) respectively for 8 weeks. After 20 weeks, the rats in group II showed notable steatosis, lobular inflammation, fibrosis accompanied with elevated (P < 0.05) serum alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (γ-GT), cholesterol, triglycerides, LDL, VLDL, leptin, tumor necrosis factor (TNF-α), transforming growth factor (TGF-β1) and hepatic malondialdehyde (MDA) compared with group I. Meanwhile, hepatic superoxide dismutase (SOD), glutathione GSH with serum HDL, adiponectin were significantly decreased (P < 0.05). These changes were to a less extent in group III. MTF or NAC individually resulted in improvement of most of these biochemical and histological parameters. These improvements were more pronounced in the combined groups VIII and IX versus each drug alone. NAC supplementation concomitant with MTF could be beneficial for the treatment of NAFLD and prevention of nonalcoholic steatohepatitis (NASH).

Published
2016

4. Hepatoprotective and Antioxidant Effect of Bauhinia hookeri Extract against Carbon Tetrachloride-Induced Hepatotoxicity in Mice and Characterization of Its Bioactive Compounds by HPLC-PDA-ESI-MS/MS

Author

Abdel-Nasser A. Sabra, Sayed H. Seif el-Din, Naglaa M. El-Lakkany, Olfat Hammam, Eman Al-Sayed, Olli Martiskainen, and Mohamed M. Abdel-Daim

Subjects
Antioxidant, Article Subject, medicine.medical_treatment, Glutathione reductase, lcsh:Medicine, Pharmacology, digestive system, General Biochemistry, Genetics and Molecular Biology, Antioxidants, Superoxide dismutase, Lipid peroxidation, chemistry.chemical_compound, Mice, Tandem Mass Spectrometry, medicine, Animals, Carbon Tetrachloride, Chromatography, High Pressure Liquid, Liver injury, chemistry.chemical_classification, General Immunology and Microbiology, biology, Chemistry, Carbon Tetrachloride Poisoning, Plant Extracts, Glutathione peroxidase, lcsh:R, General Medicine, Glutathione, medicine.disease, Malondialdehyde, Oxidative Stress, Biochemistry, Bauhinia, biology.protein, Lipid Peroxidation, Chemical and Drug Induced Liver Injury, Phytotherapy, Research Article
Abstract

The hepatoprotective and antioxidant activity ofBauhinia hookeriethanol extract (BHE) against CCl4-induced liver injury was investigated in mice. BHE was administered (500 and 1000 mg/kg/day) along with CCl4for 6 weeks. The hepatic marker enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were determined in the serum. The antioxidant parameters: glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST), and malondialdehyde (MDA) were estimated in the liver homogenate. BHE treatment significantly inhibited the CCl4-induced increase in ALT (44 and 64%), AST (36 and 46%), ALP (28 and 42%), and MDA (39 and 51%) levels at the tested doses, respectively. Moreover, BHE treatment markedly increased the activity of antioxidant parameters GSH, GPx, GR, GST, and SOD. Histological observations confirmed the strong hepatoprotective activity. These results suggest that a dietary supplement of BHE could exert a beneficial effect against oxidative stress and various liver diseases by enhancing the antioxidant defense status, reducing lipid peroxidation, and protecting against the pathological changes of the liver. The hepatoprotective activity of BHE is mediated, at least in part, by the antioxidant effect of its constituents. The active constituents of BHE were identified by HPLC-PDA-ESI/MS/MS.

Published
2014

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