Browsing by Author "Correia, Joao Francisco"

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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%).