Zirconium catalyzed synthesis of 2-arylidene Indan-1,3-diones and evaluation of their inhibitory activity against NS2B-NS3 WNV protease

dc.creatorOliveira, Ana Flávia C. da S.
dc.creatorSouza, Ana Paula M. de
dc.creatorOliveira, André S. de
dc.creatorSilva, Milene L. da
dc.creatorOliveira, Fabrício M. de
dc.creatorSantos, Edjon G.
dc.creatorSilva, Ítalo Esposti P. da
dc.creatorFerreira, Rafaela S.
dc.creatorVillela, Filipe S.
dc.creatorMartins, Felipe T.
dc.creatorLeal, Daniel H.S.
dc.creatorVaz, Boniek G.
dc.creatorTeixeira, Róbson R.
dc.creatorPaula, Sergio O. de
dc.date2018-05-18T12:04:00Z
dc.date2018-05-18T12:04:00Z
dc.date2018-04-10
dc.date.accessioned2023-09-27T20:43:37Z
dc.date.available2023-09-27T20:43:37Z
dc.identifier02235234
dc.identifierhttps://doi.org/10.1016/j.ejmech.2018.02.037
dc.identifierhttp://www.locus.ufv.br/handle/123456789/19681
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8946460
dc.descriptionA simple and efficient Knoevenagel procedure for the synthesis of 2-arylidene indan-1,3-diones is herein reported. These compounds were prepared via ZrOCl2·8H2O catalyzed reactions of indan-1,3-dione with several aromatic aldehydes and using water as the solvent. The 2-arylidene indan-1,3-diones were obtained with 53%-95% yield within 10–45 min. The synthesized compounds were evaluated as inhibitors of the NS2B-NS3 protease of West Nile Virus (WNV). It was found that hydroxylated derivatives impaired enzyme activity with varying degrees of effectiveness. The most active hydroxylated derivatives, namely 2-(4-hydroxybenzylidene)-1H-indene-1,3(2H)-dione (14) and 2-(3,4-dihydroxybenzylidene)-1H-indene-1,3(2H)-dione (17), were characterized as noncompetitive enzymes inhibitors, with IC50 values of 11 μmol L−1 and 3 μmol L−1, respectively. Docking and electrostatic potential surfaces investigations provided insight on the possible binding mode of the most active compounds within an allosteric site.
dc.formatpdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherEuropean Journal of Medicinal Chemistry
dc.relationv. 149, p. 98-109, April 2018
dc.rightsElsevier Masson SAS.
dc.subjectAntiviral agents
dc.subjectWest Nile Virus
dc.subjectIndan-1,3-dione
dc.subjectKnoevenagel condensation
dc.titleZirconium catalyzed synthesis of 2-arylidene Indan-1,3-diones and evaluation of their inhibitory activity against NS2B-NS3 WNV protease
dc.typeArtigo


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