Identification of novel urease inhibitors: pharmacophore modeling, virtual screening and molecular docking studies
| Autor: | Upasana Issar, Rita Kakkar, Richa Arora |
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| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular Quantitative structure–activity relationship 030303 biophysics Quantitative Structure-Activity Relationship Hydroxamic Acids Helicobacter Infections 03 medical and health sciences Structural Biology Urease Inhibitors Catalytic Domain Humans Computer Simulation Enzyme Inhibitors Molecular Biology 0303 health sciences Virtual screening biology Helicobacter pylori Chemistry Active site General Medicine Combinatorial chemistry Urease Molecular Docking Simulation Drug Design Lipinski's rule of five biology.protein Pharmacophore |
| DOI: | 10.6084/m9.figshare.7504751 |
| Popis: | Pharmacophore modeling and atom-based three-dimensional quantitative structure–activity relationship (3D-QSAR) have been developed on N-acylglycino- and hippurohydroxamic acid derivatives, which are known potential inhibitors of urease. This is followed by virtual screening and ADMET (absorption, distribution, metabolism, excretion and toxicity) studies on a large library of known drugs in order to get lead molecules as Helicobacter pylori urease inhibitors. A suitable three-featured pharmacophore model comprising one H-bond acceptor and two H-bond donor features (ADD.10) has been found to be the best QSAR model. An external library of compounds (∼3000 molecules), pre-filtered using Lipinski’s rule of five, has been further screened using the pharmacophore model ADD.10. By analyzing the fitness of the hits with respect to the pharmacophore model and their binding interaction inside the urease active site, four molecules have been predicted to be extremely good urease inhibitors. Two of these have significant potential and should be taken up for further drug-designing process. |
| Databáze: | OpenAIRE |
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