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

Pierre Vandurm, Christine Cauvin, Allan Guiguen, Benoît Georges, Kiet Le Van, Valérie Martinelli, Christelle Cardona, Gladys Mbemba, Jean François Mouscadet, László Hevesi, Carine Van Lint, Johan Wouters

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Résumé

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°). Docking studies suggest binding modes in agreement with structure-activity relationships.

langue originaleAnglais
Pages (de - à)4806-4809
Nombre de pages4
journalBioorganic & Medicinal Chemistry Letters
Volume19
Numéro de publication16
Les DOIs
étatPublié - 15 août 2009

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