Browsing by Author "Rios, David"

Now showing 1 - 3 of 3
  • No Thumbnail Available
    Item
    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%).
  • Thumbnail Image
    Item
    Synthesis and Antitumor Evaluation of 6-Aryl-substituted benzo[j]phenanthridine- and Benzo[g]pyrimido[4,5-c]isoquinolinequinones
    (MDPI, 2012) Iribarra, Jennyfer; Vasquez, David; Theoduloz, Cristina; Benites, Julio; Rios, David; Valderrama, Jaime A.
    A variety of novel 6-arylsubstituted benzo[j]phenanthridine-and benzo[g]pyrimido[4,5-c]isoquinolinequinones were synthesized from 1,4-naphthoquinone, aryl-aldehydes and enaminones via a two-step synthetic approach. The cytotoxic activity of the aminoquinone derivatives was evaluated in vitro against one normal cell line (MRC-5 lung fibroblasts) and three human cancer cell lines (AGS human gastric adenocarcinoma; SK-MES-1 human lung cancer cells, and J82 human bladder carcinoma) in 72-h drug exposure assays using the MTT colorimetric method. Structure-activity relationships within the series of angular quinones reveal that the insertion of pyrrol-2-yl and furan-2-yl groups at the 6-position is more significant for the increase of the potency and selectivity index of the pharmacophores.
  • Thumbnail Image
    Item
    The solar-chemical photo-Friedel-Crafts heteroacylation of 1,4-quinones
    (PERGAMON-ELSEVIER SCIENCE LTD, 2011) Benites, Julio; Rios, David; Diaz, Pilar; Valderrama, Jaime A.
    Photochemical reactions between 1,4-benzo- and 1,4-naphthoquinone and several heteroaromatic carbaldehydes were investigated under solar irradiation conditions. These reactions gave the corresponding heteroacylated hydroquinones in the range 71%-92% yield. (C) 2010 Elsevier Ltd. All rights reserved.