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
Rok vydání: 2009
Předmět:
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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