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Type: Artigo de periódico
Title: Growth Inhibitory Effects Of 3'-nitro-3-phenylamino Nor-beta-lapachone Against Hl-60: A Redox-dependent Mechanism
Author: Araujo A.J.
de Souza A.A.
da Silva Junior E.N.
Marinho-Filho J.D.B.
de Moura M.A.B.F.
Rocha D.D.
Vasconcellos M.C.
Costa C.O.
Pessoa C.
de Moraes M.O.
Ferreira V.F.
de Abreu F.C.
Pinto A.V.
Montenegro R.C.
Costa-Lotufo L.V.
Goulart M.O.F.
Abstract: In this study, the cytotoxicity, genotoxicity and early ROS generation of 2,2-dimethyl-(3H)-3-(N-3'-nitrophenylamino)naphtho[1,2-b]furan-4,5-dione (QPhNO 2) were investigated and compared with those of its precursor, nor-beta-lapachone (nor-beta), with the main goal of proposing a mechanism of antitumor action. The results were correlated with those obtained from electrochemical experiments held in protic (acetate buffer pH 4.5) and aprotic (DMF/TBABF 4) media in the presence and absence of oxygen and with those from dsDNA biosensors and ssDNA in solution, which provided evidence of a positive interaction with DNA in the case of QPhNO 2. QPhNO 2 caused DNA fragmentation and mitochondrial depolarization and induced apoptosis/necrosis in HL-60 cells. Pre-treatment with N-acetyl-l-cysteine partially abolished the observed effects related to the QPhNO 2 treatment, including those involving apoptosis induction, indicating a partially redox-dependent mechanism. These findings point to the potential use of the combination of pharmacology and electrochemistry in medicinal chemistry. © 2012 Elsevier Ltd.
Rights: fechado
Identifier DOI: 10.1016/j.tiv.2012.02.003
Date Issue: 2012
Appears in Collections:Unicamp - Artigos e Outros Documentos

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