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2000 | 47 | 1 | 11-22
Article title

Tautomers of styrylquinoline derivatives containing a methoxy substituent: Computation of their population in aqueous solution and their interaction with RSV integrase catalytic core.

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Abstracts
EN
8-Hydroxy-2-[2-(3-hydroxy-4-methoxyphenyl)ethenyl]-7-quinoline carboxylic acid and 8-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethenyl]-7-quinoline carboxylic acid inhibit the processing and strand transfer reactions catalyzed by HIV-1 integrase with an IC50 of 2 μM. Some of their spectral properties are briefly reported. Their fluorescence is so weak that it is of no use in an experimental determination of the binding to the protein and we resorted to computer simulation. Both styrylquinoline derivatives, in their monoanionic form, have several dozens of tautomers and each of these forms has four planar rotamers. In this work computer simulations have been performed to determine which tautomer is the most abundant in aqueous solution and which binds to the Rous sarcoma virus (RSV) integrase catalytic core. As the substituents on the quinoline moiety are the same as on salicylic acid, the energies of hydroxy benzoic acid tautomers were also computed both in vacuo and embedded in a continuous medium which had the dielectric constant of bulk water, using the recent CPCM technique. The CPCM method was then applied to the two integrase inhibitors to estimate the tautomer population in water. The binding site of the compounds on the RSV integrase catalytic core was determined through a docking protocol, consisting of coupling a grid search method with full energy minimization. The designed method is a way leading to identification of potent integrase inhibitors using in silico experiments.
Publisher

Year
Volume
47
Issue
1
Pages
11-22
Physical description
Dates
published
2000
received
1999-10-25
Contributors
  • Laboratoire de Physicochimie et de Pharmacologie des Macromolécules Biologiques, CNRS UMR 8532, LBPA, Ecole Normale Supérieure de Cachan, 61 avenue du Président Wilson, 94235 Cachan, France
  • Laboratoire de Physicochimie et de Pharmacologie des Macromolécules Biologiques, CNRS UMR 8532, LBPA, Ecole Normale Supérieure de Cachan, 61 avenue du Président Wilson, 94235 Cachan, France
author
  • CNRS UMR 8532, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France
author
  • Laboratoire de Physicochimie et de Pharmacologie des Macromolécules Biologiques, CNRS UMR 8532, LBPA, Ecole Normale Supérieure de Cachan, 61 avenue du Président Wilson, 94235 Cachan, France
author
  • Laboratoire de Physicochimie et de Pharmacologie des Macromolécules Biologiques, CNRS UMR 8532, LBPA, Ecole Normale Supérieure de Cachan, 61 avenue du Président Wilson, 94235 Cachan, France
  • Unité de Chimie Organique, CNRS UPRES A 8076, Centre d'Etudes Pharmaceutiques, 5 rue J.B. Clément, Université de Paris Sud, 92296 Chatenay Malabry, France
  • Unité de Chimie Organique, CNRS UPRES A 8076, Centre d'Etudes Pharmaceutiques, 5 rue J.B. Clément, Université de Paris Sud, 92296 Chatenay Malabry, France
author
  • Unité de Chimie Organique, CNRS UPRES A 8076, Centre d'Etudes Pharmaceutiques, 5 rue J.B. Clément, Université de Paris Sud, 92296 Chatenay Malabry, France
  • CNRS UMR 8532, Institut Gustave Roussy, PRII, 39 rue Camille Desmoulins, 94805 Villejuif, France
  • CNRS UMR 8532, Institut Gustave Roussy, PRII, 39 rue Camille Desmoulins, 94805 Villejuif, France
author
  • Laboratoire de Physicochimie et de Pharmacologie des Macromolécules Biologiques, CNRS UMR 8532, LBPA, Ecole Normale Supérieure de Cachan, 61 avenue du Président Wilson, 94235 Cachan, France
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bwmeta1.element.bwnjournal-article-abpv47i1p11kz
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