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Partager le résultat de cette recherche Interroger des sources externesRecherche in silico de nouveaux composés bioactifs et applications à l’inhibition de la méthionine aminopeptidase. / Hanane Boucherit
Titre : Recherche in silico de nouveaux composés bioactifs et applications à l’inhibition de la méthionine aminopeptidase. Type de document : texte imprimé Auteurs : Hanane Boucherit, Auteur ; Abdelouahab Chikhi, Directeur de thèse Mention d'édition : 15/10/2020 Editeur : جامعة الإخوة منتوري قسنطينة Année de publication : 2020 Importance : 189 f. Format : 30 cm. Note générale : 1 copies imprimées disponibles
Langues : Français (fre) Catégories : Français - Anglais
BiologieTags : Biochimie et Biologie Cellulaire et Moléculaire: Biochimie Appliquée Criblage virtuel FlexX chimiothèque ZINC méthionine aminopeptidase agents antimicrobiens Virtual screening Zinc database Methionine aminopeptidase antibacterial agents الفحص الطاهري Flexx قاعدة البيانات زنك للمرات الكينية الميثيونين أميتوببتيداز مضادات الميكروبات Index. décimale : 570 Sciences de la vie. Biologie Résumé :
The great emergence of multi-resistant pathogenic microorganisms, due to the misuse and inappropriate use of antibiotics, poses a particularly serious public health problem. Indeed, the resistance of bacteria to antibiotics sometimes makes the therapeutic treatment ineffective, and puts the practitioner in difficult situations, especially when the life of the patient is involved. The solution of this problem is therefore urgent and requires the search for new antimicrobial agents. As such, methionine aminopeptidase (MetAP) is used as an attractive target for developing new antibiotics because it is essential for bacterial survival. MetAP is a metalloprotease that cleaves N-terminal methionine during protein synthesis, a critical step in protein maturation. This work focuses on the in silico virtual screening of the commercial ZINC database to discover inhibitors with higher inhibitory activity against bacterial MetAP. Two filtering operations from the ZINC database have made it possible to retain 200 000 compounds, allowed the 3.700.000 structures proposed, for a virtual screening by FlexX. After this screening, nine chemical compounds of the top hits predicted were purchased and evaluated in vitro. The antimicrobial activity of each MetAP inhibitor was tested by the disc-diffusion assay against two Gram-positive bacteria (Staphylococcus aureus and Mycobacterium smegmatis) and two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Among the studied compounds, inhibitors ZINC04785369 and ZINC03307916 showed promising antibacterial activity. To further characterize their efficacy, the minimum inhibitory concentration was determined for each compound by the microdilution method which showed significant results. These results suggest that ZINC04785369 and ZINC03307916 are promising molecules for the development of new inhibitors of bacterial MetAP.
Note de contenu : Annexes. Diplôme : Doctorat en sciences En ligne : ../theses/biologie/BOU7678.pdf Format de la ressource électronique : Permalink : index.php?lvl=notice_display&id=11512 Recherche in silico de nouveaux composés bioactifs et applications à l’inhibition de la méthionine aminopeptidase. [texte imprimé] / Hanane Boucherit, Auteur ; Abdelouahab Chikhi, Directeur de thèse . - 15/10/2020 . - جامعة الإخوة منتوري قسنطينة, 2020 . - 189 f. ; 30 cm.
1 copies imprimées disponibles
Langues : Français (fre)
Catégories : Français - Anglais
BiologieTags : Biochimie et Biologie Cellulaire et Moléculaire: Biochimie Appliquée Criblage virtuel FlexX chimiothèque ZINC méthionine aminopeptidase agents antimicrobiens Virtual screening Zinc database Methionine aminopeptidase antibacterial agents الفحص الطاهري Flexx قاعدة البيانات زنك للمرات الكينية الميثيونين أميتوببتيداز مضادات الميكروبات Index. décimale : 570 Sciences de la vie. Biologie Résumé :
The great emergence of multi-resistant pathogenic microorganisms, due to the misuse and inappropriate use of antibiotics, poses a particularly serious public health problem. Indeed, the resistance of bacteria to antibiotics sometimes makes the therapeutic treatment ineffective, and puts the practitioner in difficult situations, especially when the life of the patient is involved. The solution of this problem is therefore urgent and requires the search for new antimicrobial agents. As such, methionine aminopeptidase (MetAP) is used as an attractive target for developing new antibiotics because it is essential for bacterial survival. MetAP is a metalloprotease that cleaves N-terminal methionine during protein synthesis, a critical step in protein maturation. This work focuses on the in silico virtual screening of the commercial ZINC database to discover inhibitors with higher inhibitory activity against bacterial MetAP. Two filtering operations from the ZINC database have made it possible to retain 200 000 compounds, allowed the 3.700.000 structures proposed, for a virtual screening by FlexX. After this screening, nine chemical compounds of the top hits predicted were purchased and evaluated in vitro. The antimicrobial activity of each MetAP inhibitor was tested by the disc-diffusion assay against two Gram-positive bacteria (Staphylococcus aureus and Mycobacterium smegmatis) and two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Among the studied compounds, inhibitors ZINC04785369 and ZINC03307916 showed promising antibacterial activity. To further characterize their efficacy, the minimum inhibitory concentration was determined for each compound by the microdilution method which showed significant results. These results suggest that ZINC04785369 and ZINC03307916 are promising molecules for the development of new inhibitors of bacterial MetAP.
Note de contenu : Annexes. Diplôme : Doctorat en sciences En ligne : ../theses/biologie/BOU7678.pdf Format de la ressource électronique : Permalink : index.php?lvl=notice_display&id=11512 Exemplaires (1)
Code-barres Cote Support Localisation Section Disponibilité BOU/7678 BOU/7678 Thèse Bibliothèque principale Thèses Disponible
Titre : Calculs et modélisations des intéractions peptide déformylase-substances antibacteriennes à l'aide de techniques de " Docking" (arrimage) moléculaire Type de document : texte imprimé Auteurs : Abdelouahab Chikhi, Auteur ; Univ. de Constantine, Éditeur scientifique ; Mustapha Bencharif, Directeur de thèse Année de publication : 2007 Importance : 123 f. Note générale : 01 Disponible à la salle de recherche 02 Disponibles au magazin de la B.U.C. 01 CD Langues : Français (fre) Catégories : Français - Anglais
BiologieTags : Modélisations Peptide déformylase Substances antibacteriennes Intéractions Docking Flex Surflex Modelling peptide deformylase antibiotic substances interactions docking FlexX Index. décimale : 570 Sciences de la vie. Biologie Résumé : The computer tool is currently requisite in research in biology to treat the stream of data
produced and to optimize its progress. The molecular stowage or '' docking '' is, indeed,
one of the methods commonly used in pharmacochimistry to discover and to finalize of
new medicines by screening of thousands of compounds for a protein target. The two
programs of molecular stowage, Surflex and FlexX, have been developed to help towards
the clarification of molecules with therapeutic activity. They proved to be effective enough
to reproduce the experimental tests because 88,4 % of the values of RMSD are lower
than 2 Å for the first one and 80,6 % for the second. They were used to study the inhibition
of the 1bsj, a peptide deformylase belonging to Escherichia coli, by diverse molecules of
ligands to discover the best inhibitors of the enzyme; this last one being found at most of
the pathogenic microorganisms. The results are comparable, generally, for both programs.
The first study highlighted the actinonin as the better inhibitor of the enzyme. Mono and bi
substitutions realized on the actinonin showed that it is possible to increase, in a
significant way, the affinity of the actinonin and its energy of interaction with the enzyme
by a well-judged choice of fragments to replace. Indeed, the replacement of the ethyl in
position 9, positioned at P1' region, by an amide and the pentyl, located at P3' region, by a
phenyl in the actinonin increase the affinity of more than 2 units (6.97 - 9.33) and the
energy of interaction of 10 units (-31.880 to -41.141 Kj / mole). The second study allowed
to identify the isoxazole-3-hydroxamic acid and its by-products as of new no peptidic
inhibitors of the 1bsj. Finally, the indole and its by-products, a new class of inhibitors
acting specifically on the bacterial PDF, presented satisfactory values of affinities with the
1Lry and the 1Lqy.Diplôme : Doctorat En ligne : ../theses/biologie/CHI4998.pdf Permalink : index.php?lvl=notice_display&id=1746 Calculs et modélisations des intéractions peptide déformylase-substances antibacteriennes à l'aide de techniques de " Docking" (arrimage) moléculaire [texte imprimé] / Abdelouahab Chikhi, Auteur ; Univ. de Constantine, Éditeur scientifique ; Mustapha Bencharif, Directeur de thèse . - 2007 . - 123 f.
01 Disponible à la salle de recherche 02 Disponibles au magazin de la B.U.C. 01 CD
Langues : Français (fre)
Catégories : Français - Anglais
BiologieTags : Modélisations Peptide déformylase Substances antibacteriennes Intéractions Docking Flex Surflex Modelling peptide deformylase antibiotic substances interactions docking FlexX Index. décimale : 570 Sciences de la vie. Biologie Résumé : The computer tool is currently requisite in research in biology to treat the stream of data
produced and to optimize its progress. The molecular stowage or '' docking '' is, indeed,
one of the methods commonly used in pharmacochimistry to discover and to finalize of
new medicines by screening of thousands of compounds for a protein target. The two
programs of molecular stowage, Surflex and FlexX, have been developed to help towards
the clarification of molecules with therapeutic activity. They proved to be effective enough
to reproduce the experimental tests because 88,4 % of the values of RMSD are lower
than 2 Å for the first one and 80,6 % for the second. They were used to study the inhibition
of the 1bsj, a peptide deformylase belonging to Escherichia coli, by diverse molecules of
ligands to discover the best inhibitors of the enzyme; this last one being found at most of
the pathogenic microorganisms. The results are comparable, generally, for both programs.
The first study highlighted the actinonin as the better inhibitor of the enzyme. Mono and bi
substitutions realized on the actinonin showed that it is possible to increase, in a
significant way, the affinity of the actinonin and its energy of interaction with the enzyme
by a well-judged choice of fragments to replace. Indeed, the replacement of the ethyl in
position 9, positioned at P1' region, by an amide and the pentyl, located at P3' region, by a
phenyl in the actinonin increase the affinity of more than 2 units (6.97 - 9.33) and the
energy of interaction of 10 units (-31.880 to -41.141 Kj / mole). The second study allowed
to identify the isoxazole-3-hydroxamic acid and its by-products as of new no peptidic
inhibitors of the 1bsj. Finally, the indole and its by-products, a new class of inhibitors
acting specifically on the bacterial PDF, presented satisfactory values of affinities with the
1Lry and the 1Lqy.Diplôme : Doctorat En ligne : ../theses/biologie/CHI4998.pdf Permalink : index.php?lvl=notice_display&id=1746 Exemplaires (1)
Code-barres Cote Support Localisation Section Disponibilité CHI/4998 CHI/4998 Thèse Bibliothèque principale Thèses Disponible
Titre : Etude comparative de l’efficacité de deux programmes de docking et application à l’inhibition de la neuraminidase Type de document : texte imprimé Auteurs : Khadidja Soulef Hioual, Auteur ; Abdelouahab Chikhi, Directeur de thèse Editeur : Constantine : Université Mentouri Constantine Année de publication : 2012 Importance : 108 f. Format : 31 cm. Note générale : Magister
2 copies imprimées disponiblesLangues : Français (fre) Catégories : Français - Anglais
BiologieTags : programmes d’amarrage protéine-ligand comparaisons RMSD GOLD FlexX précision docking liaisons rotables faux positifs neuraminidaseN1 zanamivir similaire Index. décimale : 570 Sciences de la vie. Biologie En ligne : ../theses/biologie/HIO6122.pdf Format de la ressource électronique : Permalink : index.php?lvl=notice_display&id=6026 Etude comparative de l’efficacité de deux programmes de docking et application à l’inhibition de la neuraminidase [texte imprimé] / Khadidja Soulef Hioual, Auteur ; Abdelouahab Chikhi, Directeur de thèse . - Constantine : Université Mentouri Constantine, 2012 . - 108 f. ; 31 cm.
Magister
2 copies imprimées disponibles
Langues : Français (fre)
Catégories : Français - Anglais
BiologieTags : programmes d’amarrage protéine-ligand comparaisons RMSD GOLD FlexX précision docking liaisons rotables faux positifs neuraminidaseN1 zanamivir similaire Index. décimale : 570 Sciences de la vie. Biologie En ligne : ../theses/biologie/HIO6122.pdf Format de la ressource électronique : Permalink : index.php?lvl=notice_display&id=6026 Exemplaires (1)
Code-barres Cote Support Localisation Section Disponibilité HIO/6122 HIO/6122 Thèse Bibliothèque principale Thèses Disponible
Titre : Etude in silico de l’inhibition de la peptide déformylase Type de document : texte imprimé Auteurs : Amina Merzoug, Auteur ; Abdelouahab Chikhi, Directeur de thèse Editeur : Constantine : Université Mentouri Constantine Année de publication : 2012 Importance : 80 f. Format : 31 cm. Note générale : Magister
2 copies imprimées disponiblesLangues : Français (fre) Catégories : Français - Anglais
BiologieTags : Résistance bactérienne Antibiotique Peptide déformylase Docking moléculaire Interaction protéine-ligand FlexX La règle de Lipinski Index. décimale : 570 Sciences de la vie. Biologie En ligne : ../theses/biologie/MER6106.pdf Format de la ressource électronique : Permalink : index.php?lvl=notice_display&id=6031 Etude in silico de l’inhibition de la peptide déformylase [texte imprimé] / Amina Merzoug, Auteur ; Abdelouahab Chikhi, Directeur de thèse . - Constantine : Université Mentouri Constantine, 2012 . - 80 f. ; 31 cm.
Magister
2 copies imprimées disponibles
Langues : Français (fre)
Catégories : Français - Anglais
BiologieTags : Résistance bactérienne Antibiotique Peptide déformylase Docking moléculaire Interaction protéine-ligand FlexX La règle de Lipinski Index. décimale : 570 Sciences de la vie. Biologie En ligne : ../theses/biologie/MER6106.pdf Format de la ressource électronique : Permalink : index.php?lvl=notice_display&id=6031 Exemplaires (1)
Code-barres Cote Support Localisation Section Disponibilité MER/6106 MER/6106 Thèse Bibliothèque principale Thèses Disponible
