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Acta Mathematica Scientia 2012年第3期32卷 942-954页

作者： Fatma fakhfakh Maher Mnif d'epartement de Math'ematiques Universit'e de SfaxFacult'e des Sciences de SfaxRoute de SoukraKm 3.5B.P.11713000 SfaxTunisie

In this article, we study characterization, stability, and spectral mapping the- orem for Browder＇s essential spectrum, Browder＇s essential defect spectrum and Browder＇s essential approximate point spectrum of clos... 详细信息

关键词： Browder and semi-Browder operators Browder's essential spectrum Browder's essential defect spectrum Browder's essential approximate point spectrum

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Severe Wolfram Syndrome Caused by a Novel Frameshift Mutation in <i>WFS1</i>Gene: Effect on the WFS1/CaM Interaction and Phenotype-Genotype Correlation

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Open Journal of Genetics 2021年第4期11卷 77-92页

作者： Mouna Tabebi Rahma Felhi Houcem Elomma Mrabet Wajdi Safi Baha Zantour Mohamed Habib Sfar Mohammed Abid Mouna Mnif Feki Faiza fakhfakh Laboratory of Molecular and Functional Genetics Faculty of Science University of Sfax Tunisia Laboratory of Human Molecular Genetics Faculty of Medicine University of Sfax Tunisia department of Endocrinology Tahar Sfar Hospital Mahdia Tunisia department of Endocrinology Hedi Chaker Hospital Sfax Tunisia

Mutations in the WFS1 gene have been reported in Wolfram syndrome (WFS), a rare and autosomal recessive disorder defined by early onset of diabetes mellitus and progressive optic and hearing impairment. Only few data are available concerning the association between clinical and molecular aspects of the WFS. We present a consanguineous family with a patient presenting an early onset of WFS and severe manifestations. Sequencing of WFS1 gene was performed for all the family members to search for responsible mutation and bioinformatics tools were conducted to predict its effect on structure and function of the protein. We have detected a novel frameshift mutation in the proband at homozygous state and at the heterozygous state in the parents who have no WFS manifestations. In silico analysis predicted the pathogenicity of the mutation and could lead to a complete loss of its function. Thus, 3D modeling showed that the mutation abolishes the interaction of the CaM binding region to the N-terminal of WFS1 and then impairs the WFS1-CaM complex formation. Genotype-phenotype correlation study shows that the novel mutation predisposes to early onset of diabetes and severe symptoms observed in the proband. We also report the effect of the frameshift mutation on the CaM-WFS1 impaired binding, and we discuss its possible consequence in pancreatic β-cells dysfunction and its role in the early onset of diabetes. In conclusion, the combination of impaired functions of WFS1 including unproper interaction of the CaM, Cadana;">2+

关键词： Wolfram Syndrome WFS1 Frameshift Mutation WFS1-CaM Binding

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3-(Tetrazol-5-yl)-2-imino-coumarins derivatives: Synthesis, Characterization, and Evaluation on Tumor Cell Lines

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International Journal of Organic Chemistry 2021年第1期11卷 24-34页

作者： Ali Bouattour Mehdi fakhfakh Souhir Abid El-Gharbi Majdi Abid Ludovic Paquin Rémy Le Guevel Thierry Charlier Houcine Ammar Jean-Pierre Bazureau Laboratoire de Chimie Appliquée: Hétérocycles Corps Gras et Polymères Faculté des Sciences de Sfax Université de Sfax Sfax Tunisie Chemistry department College of Science and Arts Jouf University Al Qurayyat Al Jawf KSA Institut des Sciences Chimiques de Rennes ISCR UMR CNRS 6226 Campus Beaulieu Université de Rennes 1 Bat. 10A Rennes Cedex France S2Wave Platform ScanMAT UMS 2001 CNRS Campus Beaulieu Université de Rennes 1 Bat. 10A Rennes Cedex France ImPACcell Platform SFR Biosit Bat. 8 Campus Villejean Rennes Cedex France

The first report of new 3-(tetrazol-5-yl)-2-iminocoumarin derivatives is described. The title compounds were prepared in two steps and were obtained in good yields (55-93%). They have been fully characterized by 1H, 13C NMR, FTIR, UV-Visible and HRMS. They were tested for their antiproliferative activities against six representative human tumor cell lines (Huh 7-d12, Caco2, MdA-MB231, HCT 116, PC3 and NCI-H727) and HaCat keratinocytes. Among them, compound 5e was active on HCT 116 (IC50 15 μM).

关键词： 2-Iminocoumarin Tetrazole Fluorescence Tumor Cell Lines HCT 116

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Synthesis of New 2-Phenylamino-4<i>H</i>-chromene-3-carbonitrile derivatives and Their Effects on Tumor Cell Lines and against Protein Kinases

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International Journal of Organic Chemistry 2020年第2期10卷 88-103页

作者： Ali Bouattour Mehdi fakhfakh Souhir Abid Ludovic Paquin Rémy Le Guével Thierry Charlier Sandrine Ruchaud Stéphane Bach Jean-Pierre Bazureau Houcine Ammar Laboratoire de Chimie Appliquée: Hétérocycles Corps Gras et Polymères Faculté des Sciences de Sfax Université de Sfax Sfax Tunisie département de Chimie Collège des Sciences et des Arts Université de Jouf Al Qurayyat KSA Institut des Sciences Chimiques de Rennes (ISCR) UMR CNRS 6226 Université de Rennes 1 Campus de Beaulieu Rennes France S2 Wave Platform ScanMAT UMS 2001CNRS Université de Rennes 1 Campus de Beaulieu Rennes France Université de Rennes 1 ImPACcell Platform Campus Villejean Rennes France Sorbonne Universités UPMC Université Paris 06 CNRS USR3151 Protein Phosphorylation and Human Disease Unit KISSf Platform Station Biologique Place Georges Teissier Roscoff France

The synthesis of 2-phenylimino-4H-chromene-3-carbonitriles 6(a-d) in good overall yields using an efficient and practical methodology in 3 steps has been implemented in this present work. The first step was a heterocyclization between 2-hydroxybenzaldehyde 1 and propanedinitrile 2 which produced 2-iminocoumarin 3 which was submitted to nitrogen/nitrogen displacement in the presence of aromatic primary amine 4. In the third step, reduction of 5 led to the desired 2-phenylimino-4H-chromene-3-carbonitriles 6. Compounds 5(a-d) and 6(a-d) were evaluated for their potential in vitro cytotoxicity against six selected tumor cell lines (Huh7-d12, Caco2, MdA-MB231, HCT 116, PC3 and NCI-H727) and tested for their protein kinase inhibition on eight selected protein kinases. Among them, compounds 5c and 6b exhibited inhibition on HsCK1e (5c: 44% and 6b: 42% at 1 μM) and 5c for cytotoxicity on PC3 cell lines (63% at 25 μM).

关键词： Iminocoumarin 2H-benzopyran 2-Imino-2H-benzopyran 4H-chromene 2-Amino-4H-chromene Nitrogen/Nitrogen displacement Protein Kinase Inhibition Cytotoxicity

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