title: 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.
abstract: 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-butenoïc 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.
authors: Laboratoire de Chimie Biologique Structurale, Facultés Universitaires Notre-Dame de la Paix, B-5000 Namur, Belgium. pierre.vandurm@fundp.ac.be
authors: Pierre
authors: P
authors: Vandurm
authors: Christine
authors: C
authors: Cauvin
authors: Allan
authors: A
authors: Guiguen
authors: Benoît
authors: B
authors: Georges
authors: Kiet
authors: K
authors: Le Van
authors: Valérie
authors: V
authors: Martinelli
authors: Christelle
authors: C
authors: Cardona
authors: Gladys
authors: G
authors: Mbemba
authors: Jean-François
authors: JF
authors: Mouscadet
authors: László
authors: L
authors: Hevesi
authors: Carine
authors: C
authors: Van Lint
authors: Johan
authors: J
authors: Wouters
mesh_terms: D042462:4-Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002087:Butyrates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020134:Catalytic Domain; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008968:Molecular Conformation; D011485:Protein Binding; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: C543995:(6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)-4-hydroxy-2-oxo-3-butenoic acid; D042462:4-Quinolones; D002087:Butyrates; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1