Synthesis, molecular properties prediction and cytotoxic screening of 3-(2-aryl-2-oxoethyl)isobenzofuran-1(3H)-ones

dc.creatorMaia, Angélica Faleiros da Silva
dc.creatorSiqueira, Raoni Pais
dc.creatorOliveira, Fabrício Marques de
dc.creatorFerreira, Joana Gasperazzo
dc.creatorSilva, Silma Francielle da
dc.creatorCaiuby, Clarice Alves Dale
dc.creatorOliveira, Leandro Licursi de
dc.creatorPaula, Sérgio Oliveira de
dc.creatorSouza, Rafael Aparecido Carvalho
dc.creatorGuilardi, Silvana
dc.creatorBressan, Gustavo Costa
dc.creatorTeixeira, Róbson Ricardo
dc.date2018-06-04T16:33:59Z
dc.date2018-06-04T16:33:59Z
dc.date2016-04-25
dc.date.accessioned2023-09-27T20:45:50Z
dc.date.available2023-09-27T20:45:50Z
dc.identifier0960894X
dc.identifierhttps://doi.org/10.1016/j.bmcl.2016.04.065
dc.identifierhttp://www.locus.ufv.br/handle/123456789/19912
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8947383
dc.descriptionIn the present investigation, a collection of nineteen 3-(2-aryl-2-oxoethyl)isobenzofuran-1(3H)-ones was synthesized and screened for their cytotoxic activity against a panel of three leukemia cancer cell lines. The compounds were prepared via ZrOCl2·8H2O catalyzed condensation reactions between phthalaldehydic acid and different acetophenones. The reactions were carried out free of solvent and the isobenzofuran-1(3H)-ones were obtained in good yields (80–92%). The identities of the synthesized compounds were confirmed upon IR and NMR (1H and 13C) spectroscopy as well as high resolution mass spectrometry analyses. Structures of compounds 1, 4 and 16 were also investigated by X-ray analysis. The synthesized compounds were submitted to in vitro bioassays against HL-60, K562 and NALM6 cancer cell lines using MTT cytotoxicity assay. After 48 h of treatment, twelve derivatives were able to reduce cell viability and presented IC50 values equal to or below 20 μmol L−1 against at least one of the evaluated lineages. The most active compound corresponded to 3-(3-methylphenyl-2-oxoethyl)isobenzofuran-1(3H)-one (18) (IC50 values obtained for HL-60, K562 and NALM6 were, respectively, 13.5 μmol L−1, 8.83 μmol L−1, and 5.24 μmol L−1). In addition, compound 18 was capable of triggering apoptosis on NALM6 cells. All isobenzofuranones herein evaluated did not present cytotoxicity on peripheral blood mononuclear cells (PBMC), suggesting selective cytotoxic effect on leukemic cells. A computational study allowed prediction of pharmacokinetics and drug-likeness properties of the synthesized compounds. DFT calculations were performed to obtain the energy values of HOMO, LUMO, and dipole moments of isobenzofuranones.
dc.formatpdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier Bioorganic & Medicinal Chemistry Letters
dc.relationv. 26, Issue 12, p. 2810-2816, June 2016
dc.rightsElsevier Ltd.
dc.subjectIsobenzofuran-1(3H)-one
dc.subjectPhthalides
dc.subject3-(2-Aryl-2-oxoethyl)isobenzofuran-1(3H)-ones
dc.subjectCytotoxicity
dc.titleSynthesis, molecular properties prediction and cytotoxic screening of 3-(2-aryl-2-oxoethyl)isobenzofuran-1(3H)-ones
dc.typeArtigo


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