Use este identificador para citar ou linkar para este item: https://locus.ufv.br//handle/123456789/19912
Tipo: Artigo
Título: Synthesis, molecular properties prediction and cytotoxic screening of 3-(2-aryl-2-oxoethyl)isobenzofuran-1(3H)-ones
Autor(es): Maia, Angélica Faleiros da Silva
Siqueira, Raoni Pais
Oliveira, Fabrício Marques de
Ferreira, Joana Gasperazzo
Silva, Silma Francielle da
Caiuby, Clarice Alves Dale
Oliveira, Leandro Licursi de
Paula, Sérgio Oliveira de
Souza, Rafael Aparecido Carvalho
Guilardi, Silvana
Bressan, Gustavo Costa
Teixeira, Róbson Ricardo
Abstract: In 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.
Palavras-chave: Isobenzofuran-1(3H)-one
Phthalides
3-(2-Aryl-2-oxoethyl)isobenzofuran-1(3H)-ones
Cytotoxicity
Editor: Elsevier Bioorganic & Medicinal Chemistry Letters
Tipo de Acesso: Elsevier Ltd.
URI: https://doi.org/10.1016/j.bmcl.2016.04.065
http://www.locus.ufv.br/handle/123456789/19912
Data do documento: 25-Abr-2016
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