Browsing by Author "Pedrosa, Rozangela Curi"

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    Biological evaluation of donor-acceptor aminonaphthoquinones as antitumor agents
    (ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2010) Benites, Julio; Valderrama, Jaime A.; Bettega, Karina; Pedrosa, Rozangela Curi; Buc Calderon, Pedro; Verrax, Julien
    Several members of the phenylamino-1,4-naphthoquinone series were prepared in order to investigate structure-activity relationships (SAR) and to explore the antitumor effects associated with this scaffold. The cytotoxic effects of the aminoquinones (EC50) against a panel of cancer cell lines (MCF7, DU145 and T24 cells) and healthy fibroblasts (BALB/3T3) were assessed in vitro using the MTT reduction assay 48 h after drug exposure. SAR analysis of the aminonaphthoquinone series showed that insertion of a chlorine atom in the acceptor quinone nucleus and/or insertion of a methyl group at the nitrogen atom of the donor phenylamino group induced significant changes in cytotoxic activity. Quinones 7 and 9, which exhibited the highest selective indexes (5.73 and 6.29, respectively), were further characterized using the following assays: Colony formation, caspase-3 activity, and ATP content. The results showed that aminoquinone 7 strongly influenced ATP levels and impaired the proliferative capacity of T24 cells without activating caspase-3. (C) 2010 Elsevier Masson SAS. All rights reserved.
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    Substituted 3-acyl-2-phenylamino-1,4-naphthoquinones intercalate into DNA and cause genotoxicity through the increased generation of reactive oxygen species culminating in cell death
    (2014) Farias, Mirelle Sifroni; Pich, Claus Troeger; Kviecinski, Maicon Roberto; Falcao Bucker, Nadia Cristina; Felipe, Karina Bettega; Da Silva, Fabiana Ourique; Fisher Guenther, Tania Mara; Correia, Joao Francisco; Rios, David; Benites, Julio; Valderrama, Jaime A.; Buc Calderon, Pedro; Pedrosa, Rozangela Curi
    Naphthoquinones interact with biological systems by generating reactive oxygen species (ROS) that can damage cancer cells. The cytotoxicity and the antitumor activity of 3-acyl-2-phenylamino-1,4-naphthoquinones (DPB1-DPB9) were evaluated in the MCF7 human breast cancer cell line and in male Ehrlich tumor-bearing Balb/c mice. DPB4 was the most cytotoxic derivative against MCF7 cells (EC50 15 mu M) and DPB6 was the least cytotoxic one (EC50 56 mu M). The 1,4-naphthoquinone derivatives were able to cause DNA damage and promote DNA fragmentation as shown by the plasmid DNA cleavage assay (FII form). In addition, 1,4-naphthoquinone derivatives possibly interacted with DNA as intercalating agents, which was demonstrated by the changes caused in the fluorescence of the DNA-ethidium bromide complexes. Cell death of MCF7 cells induced by 3-acyl-2-phenylamino-1,4-naphthoquinones was mostly due to apoptosis. The DNA fragmentation and subsequent apoptosis may be correlated to the redox potential of the 1,4-naphthoquinone derivatives that, once present in the cell nucleus, led to the increased generation of ROS. Finally, certain 1,4-naphthoquinone derivatives and particularly DPB4 significantly inhibited the growth of Ehrlich ascites tumors in mice (73%).