1. Digital Repository-Abdel Hafid Boussouf University Center of Mila
2. Master's
3. Natural and life sciences

Title:	Application d'une approche de criblage virtuel pour la découverte de nouveaux agents antibactériens
Authors:	Insaf, Bayou,Kourteli Besma
Keywords:	Agents antibactériens, Docking moléculaire, Surflex-dock, DXR, RMSD, Filtrage ADME-Tox Antibacterial agents, Molecular docking, Surflex-dock, DXR, RMSD, ADME-Tox filtration
Issue Date:	Jun-2024
Publisher:	university centre of abdelhafid boussouf -mila-
Citation:	Spécialité : Biochimie Appliquée
Description:	The discovery of antibiotics gave rise to hope that it would one day be possible to control all infectious diseases. However, the excessive use of antibiotics leading to the increase in the number of multi-drug resistant bacteria has become a key health threat globally. This makes it necessary to develop new therapeutic strategies, based in particular on the search for new molecules capable of acting as new antibacterial agents. During this work, we relied on the treatment of bacterial infections based on the inhibition of 1-deoxy-D-xylulose 5-phosphate reducto-isomerase (DXR), an essential enzyme of the non-mevalonic pathway of synthesis of isoprenoids, in most pathogenic microorganisms. The main objective of this research is to acquire skills in molecular modeling, the most important of which is virtual screening which is based on molecular docking by Surflex-dock in order to contribute to the in silico development of new, more powerful and more selective inhibitors of DXR of Mycobacterium tuberculosis. Our results show that the Surflex-dock program is efficient enough to contribute to the development of new molecules with therapeutic activity with 94.05% of the calculated RMSD values being less than or equal to 2Å. This test was followed by a visual analysis of the superposition of Co-crystallized ligands. These tests allow us to consider Surflex-dock as a high-performance docking program. Molecular docking of a collection of 236 similar 6JB inhibitors from the PubChem chemical library highlights the compounds CID14555675, CID49801563, CID113304440 and CID60701454 as the best DXR inhibitors with affinities equal to 8.73 M-1, 8 .99 M-1, 8.20 M-1 and 8.64 M-1 respectively. Finally, the ADME-Tox filtering application provides us with positive information on the physicochemical, pharmacokinetic and toxicological properties of the proposed inhibitors.
URI:	http://dspace.centre-univ-mila.dz/jspui/handle/123456789/3857
Appears in Collections:	Natural and life sciences

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