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.

No abstract

In this work, the electrochemical behaviour of an antitumoral nitro o-quinone derivative obtained from 3-bromo-nor-beta-lapachone was studied. Cyclic voltammetric experiments, in acetonitrile solution, revealed that both quinone and nitro functions are reduced independently as quasi-reversible one-electron transfer processes in this order. Depending on the reduction potential, a radical anion or a biradical dianion is obtained. The formation of these paramagnetic species was confirmed by performing in situ Electrochemical-Electron Spin Resonance (E-ESR) experiments. Analysis of the kinetics of electron transfer associated to those electron uptake processes, in terms of the Marcus-Hush-Levich model, revealed differences in the reorganization energy (lambda((k))) for both steps (lambda((I)): 1.07-1.11 eV; lambda((II)): 1.21-1.30 eV). By evaluating the conformations of the radical and biradical systems by calculations at the BLYP//TZVP level of theory, it was found that the inner component, for the second reduction process (lambda((II))) was approximately 72% of lambda((II)), reflecting modifications in the molecular structure during the radical anion-biradical dianion transition. This change is also reflected in the differences presented by line widths of the ESR signals of both electrogenerated radical and diradical species.

No abstract

No abstract