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Title: Computational Studies And Design of Novel Molecules As Potential Glycogen Synthase Kinase Inhibitors
Researcher: Chauhan Navneet
Guide(s): Gajjar Anuradha
Keywords: Clinical Pre Clinical and Health,Pharmacology and Toxicology,Pharmacology and Pharmacy
University: Nirma University
Completed Date: 08/08/2018
Abstract: The present thesis titled Computational Studies and Design of Novel Molecules as Potential Glycogen Synthase Kinase Inhibitors is divided into 7 chapters as described in brief. newlineChapter 1 describes the disease condition associated with the over expression of GSK-3and#946; enzyme, its structure, various strategies implemented for designing selective GSK-3and#946; inhibitors and clinical status of GSK-3and#946; inhibitors. newlineChapter 2 outlines the aim and objectives of the present work. The aim of the work is to identify new chemical moieties as GSK-3and#946; inhibitors by rational drug design based on in-silico fragment-based and docking approach as well as to identify novel inhibitors via virtual screening of chemical databases. newlineChapter 3 covers detailed literature review of various class of compounds available as GSK-3and#946; inhibitors. They are further classified based on their mode of inhibition as non-ATP competitive, substrate competitive and ATP-competitive GSK-3and#946; inhibitors. A review on patent literature is also covered. newlineChapter 4 describes prediction of binding sites and druggability assessment of GSK-3and#946; by SiteMap software tool. The ligand-binding characteristics and druggability of each site of GSK-3and#946; was assessed with SiteScore (SScore) and Druggability score (Dscore) respectively. Eight sites were identified on the surface of GSK-3and#946;. The ATP-binding site (pocket 1) and allosteric site (pocket 7) were predicted as top scoring sites of GSK-3and#946;. Application of combined in-silico fragment-based and molecular docking approach yielded the design of new chemical series of allosteric pocket 7 targeted N1,3-disubstituted imidazolidin-2-one derivatives. These hits displayed strong H-bond and pi-stacking interactions with Ser236 and His173 residues. newlineApplication of virtual screening methodology based on structural features of Tideglusib; identified new heterocyclic compounds via shape-based similarity screening using ROCS followed by molecular docking, electrostatic similarity search using EON and pharmacophore feature-based searching
Appears in Departments:Institute of Pharmacy

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01_title.pdfAttached File93.19 kBAdobe PDFView/Open
02_certificate.pdf56.76 kBAdobe PDFView/Open
06_contents.pdf309.62 kBAdobe PDFView/Open
07_list_of_tables.pdf183.8 kBAdobe PDFView/Open
08_list_of_figures.pdf220.73 kBAdobe PDFView/Open
10_chapter 1.pdf408.5 kBAdobe PDFView/Open
11_chapter 2.pdf142.1 kBAdobe PDFView/Open
12_chapter 3.pdf497.46 kBAdobe PDFView/Open
13_chapter 4.pdf2.06 MBAdobe PDFView/Open
14_chapter 5.pdf1.32 MBAdobe PDFView/Open
15_chapter 6.pdf647.51 kBAdobe PDFView/Open
16_chapter 7_summary.pdf196.79 kBAdobe PDFView/Open

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