| Literature DB >> 22386657 |
A J Araújo1, A A de Souza, E N da Silva Júnior, J D B Marinho-Filho, M A B F de Moura, D D Rocha, M C Vasconcellos, C O Costa, C Pessoa, M O de Moraes, V F Ferreira, F C de Abreu, A V Pinto, R C Montenegro, L V Costa-Lotufo, M O F Goulart.
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.Entities:
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Year: 2012 PMID： 22386657 DOI： 10.1016/j.tiv.2012.02.003
Source DB: PubMed Journal: Toxicol In Vitro ISSN： 0887-2333 Impact factor: 3.500