Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor
Autor: | Allan Guiguen, Pierre Vandurm, Christine Cauvin, Valérie Martinelli, Christelle Cardona, Carine Van Lint, Jean-François Mouscadet, Johan Wouters, Laszlo Hevesi, Gladys Mbemba, Benoît Georges, Kiet Le Van |
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Rok vydání: | 2009 |
Předmět: |
Molecular model
Stereochemistry Clinical Biochemistry Molecular Conformation Pharmaceutical Science Integrase inhibitor HIV Integrase Dihedral angle Crystallography X-Ray Biochemistry Chemical synthesis Structure-Activity Relationship Catalytic Domain Drug Discovery Integrase inhibitors Humans Computer Simulation HIV Integrase Inhibitors Molecular Biology Diketone Quinolinone 4-Quinolones biology Chemistry Organic Chemistry Integrase Butyrates Enzyme inhibitor Docking (molecular) biology.protein HIV-1 Molecular Medicine Quantum Theory β-Diketo Protein Binding |
Zdroj: | Bioorganicmedicinal chemistry letters. 19(16) |
ISSN: | 1464-3405 |
Popis: | Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoic acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30 degrees ). Docking studies suggest binding modes in agreement with structure-activity relationships. |
Databáze: | OpenAIRE |
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